The beta amyloid peptide can act as a modular aggregation domain |
| |
Authors: | Link Christopher D Fonte Virginia Roberts Christine M Hiester Brian Silverman Michael A Stein Gretchen H |
| |
Institution: | aInstitute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA;bBiological Sciences, Simon Fraser University, Burnaby, Canada BC V5A 1S6;cMolecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA |
| |
Abstract: | Although there is compelling evidence that the β amyloid peptide (Aβ) can be centrally involved in Alzheimer's disease, the natural role (if any) of this peptide remains unclear. Here we use green fluorescent protein (GFP) fusions to demonstrate that the Aβ sequence, like prion domains, can act as a modular aggregation domain when terminally appended to a normally soluble protein. We find that a single amino acid substitution (Leu17 to Pro) in the β peptide sequence can abolish this cis capacity to induce aggregation. Introduction of this substitution into full-length APP (i.e., a Leu613Pro substitution in APP695) alters the processing of APP leading to the accumulation of the C99 C-terminal fragment (CTF). We suggest that in at least some aggregation disease-related proteins the presence of an aggregation domain is not “accidental”, but reflects a selected role of these domains in modulating the trafficking or metabolism of the parental protein. |
| |
Keywords: | Alzheimer's disease C elegans Transgenic Neurodegeneration γ -secretase α -secretase AICD |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|