Upregulation of eIF5B controls cell-cycle arrest and specific developmental stages

Proliferation arrest and distinct developmental stages alter and decrease general translation yet maintain ongoing translation. The factors that support translation in these conditions remain to be characterized. We investigated an altered translation factor in three cell states considered to have reduced general translation: immature Xenopus laevis oocytes, mouse ES cells, and the transition state of proliferating mammalian cells to quiescence (G0) upon growth-factor deprivation. Our data reveal a transient increase of eukaryotic translation initiation factor 5B (eIF5B), the eukaryotic ortholog of bacterial initiation factor IF2, in these conditions. eIF5B promotes 60S ribosome subunit joining and pre-40S subunit proofreading. eIF5B has also been shown to promote the translation of viral and stress-related mRNAs and can contribute indirectly to supporting or stabilizing initiator methionyl tRNA (tRNA-Met_i) association with the ribosome. We find that eIF5B is a limiting factor for translation in these three conditions. The increased eIF5B levels lead to increased eIF5B complexes with tRNA-Met_i upon serum starvation of THP1 mammalian cells. In addition, increased phosphorylation of eukaryotic initiation factor 2α, the translation factor that recruits initiator tRNA-Met_i for general translation, is observed in these conditions. Importantly, we find that eIF5B is an antagonist of G0 and G0-like states, as eIF5B depletion reduces maturation of G0-like, immature oocytes and hastens early G0 arrest in serum-starved THP1 cells. Consistently, eIF5B overexpression promotes maturation of G0-like immature oocytes and causes cell death, an alternative to G0, in serum-starved THP1 cells. These data reveal a critical role for a translation factor that regulates specific cell-cycle transition and developmental stages.Specific cell states and transitions, including distinct developmental stages and cell-cycle arrest, alter and decrease general translation (1, 2) yet exhibit ongoing translation (3). In immature Xenopus laevis oocytes, translation of mRNAs is regulated and active after maturation (3, 4); however, mRNAs are translated during immature stages preceding maturation (5). Similarly, canonical translation is altered in mouse ES cells until differentiation (6), but translation ensues in ES cells (7), indicating that uncharacterized factors operate to support general translation in these cell states.The transition from immature to mature oocytes shows some features similar to the entry into mammalian G1/cell cycle from quiescence (G0) (8), an assortment of reversible, cell-cycle–arrested states that can withstand unfavorable environments (9). Serum deprivation of proliferating mammalian cells induces an early stage of transient stress that alters gene expression; cells subjected to such stress either adapt to these nonproliferative conditions and proceed further into G0 or alternatively undergo cell death (9). Early (1 day) serum starvation represents a transient and heterogeneous state and is distinct from prolonged serum starvation in cells that have entered G0 and late G0 (9). The reprogramming of gene expression during this transition involves a decrease in overall translation, yet ongoing translation is observed (10), indicating that undiscovered factors support translation in these conditions.The mechanism of translation involves several steps, including recruitment of the initiator methionyl tRNA (tRNA-Met_i) to the small 40S ribosome subunit by eukaryotic initiation factor 2 (eIF2) and joining of the large 60S ribosome subunit by eukaryotic initiation factor 5B (eIF5B) (1, 2, 11). eIF5B is the mammalian ortholog of bacterial IF2 that is important in the formation of the 30S initiation complex, stimulates 50S association to form 70S complexes, and can contribute to stabilizing tRNA-Met_i association with the ribosome (2, 11–13). eIF5B functions in 60S ribosome subunit joining during canonical translation (2, 13, 14) and is involved in pre-40S ribosome subunit proofing (15, 16). eIF5B is also required for the translation of a few viral and specialized mRNAs (12, 17–20) and can contribute to supporting or stabilizing tRNA-Met_i association, including in specific conditions where phosphorylation of the eIF2 subunit, eIF2α, is also observed (12, 17–19). In some cases, phosphorylation of eIF2α is sufficiently increased relative to the levels of its guanine nucleotide exchange factor (eIF2B), which leads to decreased release of phosphorylated eIF2α from eIF2B. This decrease prevents the recycling of inactive eIF2α-GDP to the active eIF2α-GTP form and can cause altered translation (2, 21, 22).Here we investigated an altered translation factor in cell states considered to have reduced general translation: in late immature oocytes, in ES cells, and during the transient stress induced in the early stages of growth-factor deprivation of proliferating mammalian cells (3, 4, 6, 7, 10). We find that eIF5B is transiently increased in these three conditions. The role of eIF5B in 60S subunit joining and other functions (2, 13–16) may be important for translation in these conditions and may indirectly enable tRNA-Met_i association. Accordingly, depletion of eIF5B reduces translation, indicating that eIF5B is limiting, in part, for translation in these three conditions. In serum-starved cells, the increased levels of eIF5B lead to increased formation of eIF5B complexes with tRNA-Met_i, consistent with its previously described role with viral and stress mRNAs (12, 17–19). Additionally, increased phosphorylation of eIF2α is observed in these three conditions. Importantly, we find that eIF5B overexpression promotes the transition away from G0 or G0-like states (immature oocytes; ref. 8), enhancing the maturation of late G0-like immature oocytes and causing cell death, the alternative to G0, upon serum deprivation of proliferating mammalian cells. These data suggest that eIF5B promotes translation in these specific conditions and is an antagonist of G0 and G0-like states; consistently, eIF5B depletion decreases translation, promotes the immature state of oocytes, and enables earlier G0 arrest upon serum starvation of proliferating mammalian cells. These studies reveal a critical role for a translation factor that is important for general translation under specific conditions and regulates distinct cell and developmental stages.     

Exchange protein directly activated by cAMP plays a critical role in bacterial invasion during fatal rickettsioses

Rickettsiae are responsible for some of the most devastating human infections. A high infectivity and severe illness after inhalation make some rickettsiae bioterrorism threats. We report that deletion of the exchange protein directly activated by cAMP (Epac) gene, Epac1, in mice protects them from an ordinarily lethal dose of rickettsiae. Inhibition of Epac1 suppresses bacterial adhesion and invasion. Most importantly, pharmacological inhibition of Epac1 in vivo using an Epac-specific small-molecule inhibitor, ESI-09, completely recapitulates the Epac1 knockout phenotype. ESI-09 treatment dramatically decreases the morbidity and mortality associated with fatal spotted fever rickettsiosis. Our results demonstrate that Epac1-mediated signaling represents a mechanism for host–pathogen interactions and that Epac1 is a potential target for the prevention and treatment of fatal rickettsioses.Rickettsiae are responsible for some of the most devastating human infections (1–4). It has been forecasted that temperature increases attributable to global climate change will lead to more widespread distribution of rickettsioses (5). These tick-borne diseases are caused by obligately intracellular bacteria of the genus Rickettsia, including Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever (RMSF) in the United States and Latin America (2, 3), and Rickettsia conorii, the causative agent of Mediterranean spotted fever endemic to southern Europe, North Africa, and India (6). A high infectivity and severe illness after inhalation make some rickettsiae (including Rickettsia prowazekii, R. rickettsii, Rickettsia typhi, and R. conorii) bioterrorism threats (7). Although the majority of rickettsial infections can be controlled by appropriate broad-spectrum antibiotic therapy if diagnosed early, up to 20% of misdiagnosed or untreated (1, 3) and 5% of treated RMSF cases (8) result in a fatal outcome caused by acute disseminated vascular endothelial infection and damage (9). Fatality rates as high as 32% have been reported in hospitalized patients diagnosed with Mediterranean spotted fever (10). In addition, strains of R. prowazekii resistant to tetracycline and chloramphenicol have been developed in laboratories (11). Disseminated endothelial infection and endothelial barrier disruption with increased microvascular permeability are the central features of SFG rickettsioses (1, 2, 9). The molecular mechanisms involved in rickettsial infection remain incompletely elucidated (9, 12). A comprehensive understanding of rickettsial pathogenesis and the development of novel mechanism-based treatment are urgently needed.Living organisms use intricate signaling networks for sensing and responding to changes in the external environment. cAMP, a ubiquitous second messenger, is an important molecular switch that translates environmental signals into regulatory effects in cells (13). As such, a number of microbial pathogens have evolved a set of diverse virulence-enhancing strategies that exploit the cAMP-signaling pathways of their hosts (14). The intracellular functions of cAMP are predominantly mediated by the classic cAMP receptor, protein kinase A (PKA), and the more recently discovered exchange protein directly activated by cAMP (Epac) (15). Thus, far, two isoforms, Epac1 and Epac2, have been identified in humans (16, 17). Epac proteins function by responding to increased intracellular cAMP levels and activating the Ras superfamily small GTPases Ras-proximate 1 and 2 (Rap1 and Rap2). Accumulating evidence demonstrates that the cAMP/Epac1 signaling axis plays key regulatory roles in controlling various cellular functions in endothelial cells in vitro, including cell adhesion (18–21), exocytosis (22), tissue plasminogen activator expression (23), suppressor of cytokine signaling 3 (SOCS-3) induction (24–27), microtubule dynamics (28, 29), cell–cell junctions, and permeability and barrier functions (30–37). Considering the critical importance of endothelial cells in rickettsioses, we examined the functional roles of Epac1 in rickettsial pathogenesis in vivo, taking advantage of the recently generated Epac1 knockout mouse (38) and Epac-specific inhibitors (39, 40) generated from our laboratory. Our studies demonstrate that Epac1 plays a key role in rickettsial infection and represents a therapeutic target for fatal rickettsioses.     

Bacterial scaffold directs pole-specific centromere segregation

Bacteria use partitioning systems based on the ParA ATPase to actively mobilize and spatially organize molecular cargoes throughout the cytoplasm. The bacterium Caulobacter crescentus uses a ParA-based partitioning system to segregate newly replicated chromosomal centromeres to opposite cell poles. Here we demonstrate that the Caulobacter PopZ scaffold creates an organizing center at the cell pole that actively regulates polar centromere transport by the ParA partition system. As segregation proceeds, the ParB-bound centromere complex is moved by progressively disassembling ParA from a nucleoid-bound structure. Using superresolution microscopy, we show that released ParA is recruited directly to binding sites within a 3D ultrastructure composed of PopZ at the cell pole, whereas the ParB-centromere complex remains at the periphery of the PopZ structure. PopZ recruitment of ParA stimulates ParA to assemble on the nucleoid near the PopZ-proximal cell pole. We identify mutations in PopZ that allow scaffold assembly but specifically abrogate interactions with ParA and demonstrate that PopZ/ParA interactions are required for proper chromosome segregation in vivo. We propose that during segregation PopZ sequesters free ParA and induces target-proximal regeneration of ParA DNA binding activity to enforce processive and pole-directed centromere segregation, preventing segregation reversals. PopZ therefore functions as a polar hub complex at the cell pole to directly regulate the directionality and destination of transfer of the mitotic segregation machine.The bacterial cytoplasm is a complex mixture of dynamic macromolecules densely packed into a tiny compartment. Recent studies have revealed unexpected levels of organization of bacterial cytoplasmic components, including hundreds of proteins, specific lipids, mRNA molecules, and even the nucleoid itself (1). One strategy used by bacteria to generate subcellular organization of specific macromolecular complexes is active segregation by ParA-mediated molecular partitioning machines. ParA-based partitioning systems are found throughout bacteria and have been shown to spatially organize diverse macromolecular complexes to facilitate their equal distribution to progeny during cell division (2). An important question is how directionality is provided to ParA partitioning machines.One family of highly conserved ParA-based partitioning systems segregates plasmid or chromosomal centromeres to daughter cells during cell division. ParA-mediated DNA partitioning systems (Par systems) are composed of three core components: a centromeric DNA sequence parS, a site-specific DNA binding protein ParB that binds to the centromere parS sequence, and the ATPase ParA. Structural studies demonstrate that the activity of ParA is regulated by a molecular switch in which ATP-bound ParA forms dimers that bind tightly to DNA, and ParB stimulates ATP hydrolysis and release of ADP-bound ParA as monomers (3). During centromere partitioning in vivo, ATP-bound ParA assembles into a multimeric nucleoid-bound structure (4). At the centromere, ParB binds to the parS locus and nearby DNA to create a compact nucleoprotein complex (5). This ParB/parS complex binds to ParA subunits within the ParA/nucleoid structure, stimulating ATP hydrolysis and release of ParA-ADP (6–8). The multivalent ParB/parS complex has thus been proposed to bind to and shorten the ParA superstructure on the nucleoid, moving along a receding track via a dynamic disassembly mechanism (6, 8–10). The result of this process is the movement of the chromosomal centromere (parS) relative to the nucleoid bulk, and therefore to the cell itself.Whereas the fundamental operating principles of ParA-mediated movement seem conserved, how these machines target transfer to specific subcellular destinations is unknown. Many chromosomal Par systems maintain a single origin-proximal ParB/parS complex at the old cell pole and, after replication, move one newly replicated parS locus to the opposite pole (9, 11, 12). Polar protein complexes that interact with chromosome segregation factors have been identified in various bacteria, but the mechanistic consequences of these interactions have not been established (13–15). In Caulobacter, two distinct polar protein factors affect ParA-mediated centromere segregation: the new pole-specific protein TipN (16, 17) and the polar organizing protein PopZ (18, 19). TipN is a large, membrane-anchored, coiled-coil rich protein that localizes to the new pole throughout the cell cycle and, in addition to roles in localization of flagellar synthesis (16, 17), affects processive parS segregation via an unknown mechanism (6, 20).In contrast, PopZ is a small, acidic protein that forms a polymeric network at the cell pole (18, 19). In the prereplicative cell, PopZ localizes exclusively at the old cell pole, where it anchors the ParB-bound parS locus via direct interactions with ParB (18, 19). During chromosome replication initiation, PopZ releases ParB from the old pole and adopts a bipolar PopZ distribution that seems to capture ParB/parS complexes during the segregation process (18, 19). Whereas cells lacking tipN are only mildly elongated, popZ deletion causes severe filamentation (16–19), suggesting that PopZ plays a more important role in the regulation of segregation. However, the molecular mechanism by which PopZ affects segregation has remained elusive.Here we demonstrate that the multifunctional PopZ complex plays a crucial role in pole-directed movement of ParA-mediated chromosome segregation by interacting directly with ParA. We show that PopZ, but not TipN, is required for robust polar recruitment of ParA and demonstrate that a polar PopZ scaffold recruits and concentrates free ParA released during segregation. Recruitment of ParA within the PopZ matrix sequesters free ParA and locally regenerates ParA DNA binding activity. Active ParA complexes are released for recycling into nucleoid-bound structures near the cell pole, which we propose drives centromere segregation toward pole-localized PopZ. Thus, PopZ orchestrates a positive feedback mechanism that forces ParA-mediated centromere transfer to the cell pole. The polar PopZ scaffold complex creates a unique 3D microenvironment at the pole that spatially separates distinct centromere tethering and ParA-modulation activities, enabling coupling between chromosome segregation with the initiation of cell division.     

Reactivation of stalled polyribosomes in synaptic plasticity

Some forms of synaptic plasticity require rapid, local activation of protein synthesis. Although this is thought to reflect recruitment of mRNAs to free ribosomes, this would limit the speed and magnitude of translational activation. Here we provide compelling in situ evidence supporting an alternative model in which synaptic mRNAs are transported as stably paused polyribosomes. Remarkably, we show that metabotropic glutamate receptor activation allows the synthesis of proteins that lead to a functional long-term depression phenotype even when translation initiation has been greatly reduced. Thus, neurons evolved a unique mechanism to swiftly translate synaptic mRNAs into functional protein upon synaptic signaling using stalled polyribosomes to bypass the rate-limiting step of translation initiation. Because dysregulated plasticity is implicated in neurodevelopmental and psychiatric disorders such as fragile X syndrome, this work uncovers a unique translational target for therapies.Most studies of translational control focus on initiation, the process where mRNAs recruit ribosomes and catalyze the first step of translation (1). This highly regulated and normally rate-limiting step of translation is followed by elongation and termination, resulting in completed proteins. Although multiple ribosomes on a given mRNA (a polyribosome) imply active peptide synthesis, we and others identified neuronal RNA granules—motile aggregates of nontranslating ribosomes (2, 3). These electron-dense bodies contain single copies of synaptic mRNAs that are translationally silenced during their transport from soma to synapse (1, 4).Many models assume that neuronally transported mRNAs are translationally paused before completion of the initiation step of translation during transport. An appropriate synaptic signal would then activate translation (initiation/elongation/termination) of the granule mRNA. However, it is not clear how many free ribosomal subunits are present at synapses to support translation initiation. Further, at a typical translation elongation rate of six amino acids per s (5, 6), synthesis of larger synaptic proteins (e.g., microtubule-associated protein 1b; MAP1b) would take over 5 min even if initiation were immediate. These two factors constrain the speed and magnitude of synaptic translation and, thus, plasticity. As some forms of synaptic plasticity require rapid (<10 min) and localized activation of protein synthesis, an alternative model is wanting (7–9).We have previously proposed the concept of a neuronal RNA granule as a stalled polyribosome (10, 11). Ribosomal stalling has been shown to occur in lysates from a mouse neuroblastoma cell line and in an in vitro rabbit reticulocyte lysate translation assay programmed with brain homogenate (12). Whether neuronal ribosome stalling occurs in vivo is uncertain. We hypothesized that neuronal RNA granules contain paused ribosomes with incomplete proteins initiated in the soma before their packaging and transport to dendrites, where translation can be rapidly and locally completed on demand. Here we show that reactivation of translation on stalled polyribosomes is a unique feature of the neuronal landscape that functions in metabotropic glutamate receptor (mGluR) long-term depression (LTD), providing the neuron with the ability to rapidly and specifically respond to stimuli independently of translation initiation.     

Structural basis for translational surveillance by the large ribosomal subunit-associated protein quality control complex

All organisms have evolved mechanisms to manage the stalling of ribosomes upon translation of aberrant mRNA. In eukaryotes, the large ribosomal subunit-associated quality control complex (RQC), composed of the listerin/Ltn1 E3 ubiquitin ligase and cofactors, mediates the ubiquitylation and extraction of ribosome-stalled nascent polypeptide chains for proteasomal degradation. How RQC recognizes stalled ribosomes and performs its functions has not been understood. Using single-particle cryoelectron microscopy, we have determined the structure of the RQC complex bound to stalled 60S ribosomal subunits. The structure establishes how Ltn1 associates with the large ribosomal subunit and properly positions its E3-catalytic RING domain to mediate nascent chain ubiquitylation. The structure also reveals that a distinguishing feature of stalled 60S particles is an exposed, nascent chain-conjugated tRNA, and that the Tae2 subunit of RQC, which facilitates Ltn1 binding, is responsible for selective recognition of stalled 60S subunits. RQC components are engaged in interactions across a large span of the 60S subunit surface, connecting the tRNA in the peptidyl transferase center to the distally located nascent chain tunnel exit. This work provides insights into a mechanism linking translation and protein degradation that targets defective proteins immediately after synthesis, while ignoring nascent chains in normally translating ribosomes.During the canonical termination and recycling steps of translation, stop codon recognition triggers factor-mediated hydrolysis of the nascent peptidyl-tRNA conjugate, nascent chain release, and ribosome splitting (1–3). Conversely, translation of aberrant mRNA, such as mRNA lacking stop codons (“nonstop mRNA”), renders 80S ribosomes stalled with nascent polypeptides (1–3). Furthermore, “nonstop proteins” cannot be corrected by quality control chaperones and have the potential to interfere with cellular function (3, 4). Not surprisingly, defective termination and recycling are under surveillance by a variety of mechanisms (1–3). In eukaryotes, “rescue factors” homologous to termination factors promote dissociation of translationally halted ribosomes in a stop codon-independent manner (5). However, because rescue factors lack peptidyl-tRNA hydrolase activity, their action results in nascent chains remaining stalled on the released 60S subunit.Ltn1 is the critical E3 ligase mediating ubiquitylation of aberrant proteins that become stalled on ribosomes during translation (4). Mutation of the Ltn1 mouse ortholog, listerin, causes neurodegeneration (6), suggesting an important function for this process. Ltn1 works together with several cofactors as part of the ribosome-associated quality control complex (RQC) (7–9) and appears to first associate with nascent chain-stalled 60S subunits together with two proteins of unknown function, Tae2 and Rqc1 (7, 9). Ltn1-mediated ubiquitylation of the stalled polypeptide then results in the recruitment of the AAA ATPase Cdc48/p97/VCP. This recruitment also requires Rqc1 and Tae2, and is followed by Cdc48-mediated nascent chain extraction and delivery to the proteasome for degradation (7–9).Exactly how RQC recognizes stalled ribosomes and performs its functions has not been understood, and the only structure available in this system is that of free Ltn1 at 40-Å resolution (10). To elucidate mechanisms underlying RQC function, we set out to solve the structure of the endogenous complex purified from yeast. To reduce sample heterogeneity so as to facilitate structural characterization, RQC assembly was blocked in a preubiquitylation step by using cells expressing endogenous Ltn1 with a deletion of the E3-catalytic RING domain (Ltn1-∆R). This Ltn1 mutant is competent for binding to 60S subunits but fails to ubiquitylate substrates (4), thus preventing downstream events from being triggered.     

Self-assembly of alkynylplatinum(II) terpyridine amphiphiles into nanostructures via steric control and metal–metal interactions

A series of mono- and dinuclear alkynylplatinum(II) terpyridine complexes containing the hydrophilic oligo(para-phenylene ethynylene) with two 3,6,9-trioxadec-1-yloxy chains was designed and synthesized. The mononuclear alkynylplatinum(II) terpyridine complex was found to display a very strong tendency toward the formation of supramolecular structures. Interestingly, additional end-capping with another platinum(II) terpyridine moiety of various steric bulk at the terminal alkyne would lead to the formation of nanotubes or helical ribbons. These desirable nanostructures were found to be governed by the steric bulk on the platinum(II) terpyridine moieties, which modulates the directional metal−metal interactions and controls the formation of nanotubes or helical ribbons. Detailed analysis of temperature-dependent UV-visible absorption spectra of the nanostructured tubular aggregates also provided insights into the assembly mechanism and showed the role of metal−metal interactions in the cooperative supramolecular polymerization of the amphiphilic platinum(II) complexes.Square-planar d⁸ platinum(II) polypyridine complexes have long been known to exhibit intriguing spectroscopic and luminescence properties (1–54) as well as interesting solid-state polymorphism associated with metal−metal and π−π stacking interactions (1–14, 25). Earlier work by our group showed the first example, to our knowledge, of an alkynylplatinum(II) terpyridine system [Pt(tpy)(C ≡ CR)]⁺ that incorporates σ-donating and solubilizing alkynyl ligands together with the formation of Pt···Pt interactions to exhibit notable color changes and luminescence enhancements on solvent composition change (25) and polyelectrolyte addition (26). This approach has provided access to the alkynylplatinum(II) terpyridine and other related cyclometalated platinum(II) complexes, with functionalities that can self-assemble into metallogels (27–31), liquid crystals (32, 33), and other different molecular architectures, such as hairpin conformation (34), helices (35–38), nanostructures (39–45), and molecular tweezers (46, 47), as well as having a wide range of applications in molecular recognition (48–52), biomolecular labeling (48–52), and materials science (53, 54). Recently, metal-containing amphiphiles have also emerged as a building block for supramolecular architectures (42–44, 55–59). Their self-assembly has always been found to yield different molecular architectures with unprecedented complexity through the multiple noncovalent interactions on the introduction of external stimuli (42–44, 55–59).Helical architecture is one of the most exciting self-assembled morphologies because of the uniqueness for the functional and topological properties (60–69). Helical ribbons composed of amphiphiles, such as diacetylenic lipids, glutamates, and peptide-based amphiphiles, are often precursors for the growth of tubular structures on an increase in the width or the merging of the edges of ribbons (64, 65). Recently, the optimization of nanotube formation vs. helical nanostructures has aroused considerable interests and can be achieved through a fine interplay of the influence on the amphiphilic property of molecules (66), choice of counteranions (67, 68), or pH values of the media (69), which would govern the self-assembly of molecules into desirable aggregates of helical ribbons or nanotube scaffolds. However, a precise control of supramolecular morphology between helical ribbons and nanotubes remains challenging, particularly for the polycyclic aromatics in the field of molecular assembly (64–69). Oligo(para-phenylene ethynylene)s (OPEs) with solely π−π stacking interactions are well-recognized to self-assemble into supramolecular system of various nanostructures but rarely result in the formation of tubular scaffolds (70–73). In view of the rich photophysical properties of square-planar d⁸ platinum(II) systems and their propensity toward formation of directional Pt···Pt interactions in distinctive morphologies (27–31, 39–45), it is anticipated that such directional and noncovalent metal−metal interactions might be capable of directing or dictating molecular ordering and alignment to give desirable nanostructures of helical ribbons or nanotubes in a precise and controllable manner.Herein, we report the design and synthesis of mono- and dinuclear alkynylplatinum(II) terpyridine complexes containing hydrophilic OPEs with two 3,6,9-trioxadec-1-yloxy chains. The mononuclear alkynylplatinum(II) terpyridine complex with amphiphilic property is found to show a strong tendency toward the formation of supramolecular structures on diffusion of diethyl ether in dichloromethane or dimethyl sulfoxide (DMSO) solution. Interestingly, additional end-capping with another platinum(II) terpyridine moiety of various steric bulk at the terminal alkyne would result in nanotubes or helical ribbons in the self-assembly process. To the best of our knowledge, this finding represents the first example of the utilization of the steric bulk of the moieties, which modulates the formation of directional metal−metal interactions to precisely control the formation of nanotubes or helical ribbons in the self-assembly process. Application of the nucleation–elongation model into this assembly process by UV-visible (UV-vis) absorption spectroscopic studies has elucidated the nature of the molecular self-assembly, and more importantly, it has revealed the role of metal−metal interactions in the formation of these two types of nanostructures.