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Please use this identifier to cite or link to this item: http://arks.princeton.edu/ark:/88435/dsp01vd66w2342
Title: The Structure of the Sec1/Munc18 Protein Vps45 Reveals Conserved Features that Support SNARE Binding
Authors: Allen, Frederick
Advisors: Hughson, Frederick M.
Department: Molecular Biology
Class Year: 2016
Abstract: Sec1/Munc18 (SM) proteins directly interact with soluble NSF attachment protein receptors (SNAREs) to positively regulate the essential process of vesicle fusion. SM proteins localize to the site of vesicle fusion where one SNARE on the vesicle and three SNAREs on the target membrane together form a four‐helix bundle that mediates membrane fusion. Although there are four classes of SM proteins, which function in different subsets of trafficking pathways, SM proteins share similar features that support SNARE binding. The SM protein class Vps45, which mediates fusion of vesicles at the late endosome, is no exception; however, lack of structural data has hindered full inclusion of Vps45 in the discussion of SM protein function. Here we present the crystal structure of Chaetomium thermophilum Vps45, resolved to 1.85 Å. Vps45 shares an overall shape, topology and structural domain distribution with the other SM proteins. Alignment of the structures of SM proteins bound to their cognate SNAREs with Vps45 reveals that Vps45 likely binds SNAREs using the same modes earlier reported for other SM proteins. Conserved surface residues cluster around the proposed SNARE binding sites on Vps45, indicating their functional importance. Notably, these findings support the hypothesis that SM proteins function as templates for the initiation of SNARE complex assembly. The crystal structure of Vps45 therefore contributes to the elucidation of SM protein function and should fuel further investigation into SNARE‐SM interactions.
Extent: 60 pages
URI: http://arks.princeton.edu/ark:/88435/dsp01vd66w2342
Type of Material: Princeton University Senior Theses
Language: en_US
Appears in Collections:Molecular Biology, 1954-2016

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