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dc.contributor.advisorHughson, Frederick M-
dc.contributor.authorShimamura, Gregory Ryan-
dc.contributor.otherMolecular Biology Department-
dc.description.abstractSNARE proteins fuse membranes. Each SNARE protein contains a SNARE domain that assembles with three partners into tetrameric complexes by forming four-helix bundles, which in turn pulls the SNAREs’ transmembrane domains, and thus the membranes they are embedded in, together leading to fusion. SNAREs alone are unable to fuse membranes with the speed and specificity observed in vivo. SM (Sec1/Munc18) family proteins and multisubunit tethering complexes interact with SNARE to stimulate membrane fusion; however, the mechanisms by which these proteins act are incompletely understood. Recent work has proposed that SM proteins function as chaperones of SNARE complex assembly. We have tested and extended this hypothesis by showing that the SM protein Vps33 functions as a bona fide catalyst of SNARE complex assembly by binding directly to SNARE domains. Vps33 increases the initial rate of SNARE complex assembly by approximately seven-fold and can perform multiple turnovers. To determine if our model applies to other SM proteins, we have produced a crystal structure of the SM protein Vps45 and have determined that it has conserved structural features homologous to the regions of Vps33 which bind to SNAREs. Vps45 is able to bind the Qa-SNARE Tlg2, and our preliminary evidence suggests that it can extract Tlg2 from nonproductive homo-multimeric SNARE complex. Finally, to better understand how multisubunit tethering complexes may function to enhance SNARE complex assembly, we have characterized interactions among the subunits of the conserved oligomeric Golgi complex and provided new structural insights into how the complex is assembled.-
dc.publisherPrinceton, NJ : Princeton University-
dc.relation.isformatofThe Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog: <a href=> </a>-
dc.titleFacilitating SNARE-mediated membrane fusion: structural and biochemical studies of SM proteins and the COG complex-
dc.typeAcademic dissertations (Ph.D.)-
Appears in Collections:Molecular Biology

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