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Title: General and Distinct Functions of Sec1/Munc18-like Protein Families
Authors: Shirai, Nanako
Advisors: Hughson, Frederick
Department: Molecular Biology
Class Year: 2021
Abstract: All eukaryotes require Sec1/Munc18-like (SM) proteins for SNARE-mediated membrane fusion. SM proteins are divided into four families that function in different trafficking pathways — Sec1/Munc18, Vps33, Vps45, and Sly1. While their general function is to stimulate membrane fusion, they also have distinct, family-specific functions. Critical to the general function of SM proteins are an anti-parallel pair of helices, called the helical hairpin. Superposition of two crystal structures of SM protein Vps33 bound to its SNAREs suggests that this helical hairpin templates the R- and Qa-SNAREs in a half-assembled SNARE complex. This mechanistic model, or ‘template model,’ could explain how SM proteins stimulate membrane fusion. It is unclear, however, (1) if the template model is conserved in all four families, and (2) if the helical hairpin also mediates family-specific functions. Here, I created sequence banks and analyzed residue conservation in each SM protein family. I show that the template model appears to be a conserved mechanism for the general function of SM proteins; in all four families, the SM protein residues that would bind the SNAREs in the template model were more significantly conserved than other solvent-exposed SM protein residues. The helical hairpin also appears to facilitate family-specific functions, since several residues on the surface of the helical hairpin were conserved family-specifically. Taken together, these results suggest that the helical hairpin facilitates both general and distinct functions of SM proteins. Future investigations of the helical hairpin will need to uncouple these general and distinct functions.
Type of Material: Princeton University Senior Theses
Language: en
Appears in Collections:Molecular Biology, 1954-2021

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