Molecular mechanism of membrane constriction and tubulation mediated by the F-BAR protein Pacsin/Syndapin |
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| Authors: | Qi Wang Marcos V. A. S. Navarro Gary Peng Evan Molinelli Shih Lin Goh Bret L. Judson Kanagalaghatta R. Rajashankar Holger Sondermann |
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| Affiliation: | aDepartment of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853; ;bWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853; and ;cNortheastern Collaborative Access Team, Building 436, Argonne National Laboratory, Argonne, IL 60439 |
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| Abstract: | Peripheral membrane proteins of the Bin/amphiphysin/Rvs (BAR) and Fer-CIP4 homology-BAR (F-BAR) family participate in cellular membrane trafficking and have been shown to generate membrane tubules. The degree of membrane bending appears to be encoded in the structure and immanent curvature of the particular protein domains, with BAR and F-BAR domains inducing high- and low-curvature tubules, respectively. In addition, oligomerization and the formation of ordered arrays influences tubule stabilization. Here, the F-BAR domain-containing protein Pacsin was found to possess a unique activity, creating small tubules and tubule constrictions, in addition to the wide tubules characteristic for this subfamily. Based on crystal structures of the F-BAR domain of Pacsin and mutagenesis studies, vesiculation could be linked to the presence of unique structural features distinguishing it from other F-BAR proteins. Tubulation was suppressed in the context of the full-length protein, suggesting that Pacsin is autoinhibited in solution. The regulated deformation of membranes and promotion of tubule constrictions by Pacsin suggests a more versatile function of these proteins in vesiculation and endocytosis beyond their role as scaffold proteins. |
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| Keywords: | endocytosis membrane trafficking protein structure |
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