Reference: Starai VJ, et al. (2008) HOPS proofreads the trans-SNARE complex for yeast vacuole fusion. Mol Biol Cell 19(6):2500-8

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Abstract


The fusion of yeast vacuoles, like other organelles, requires a Rab-family guanosine triphosphatase (Ypt7p), a Rab effector and Sec1/Munc18 (SM) complex termed HOPS (homotypic fusion and vacuole protein sorting), and soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The central 0-layer of the four bundled vacuolar SNAREs requires the wild-type three glutaminyl (Q) and one arginyl (R) residues for optimal fusion. Alterations of this layer dramatically increase the K(m) value for SNAREs to assemble trans-SNARE complexes and to fuse. We now find that added purified HOPS complex strongly suppresses the fusion of vacuoles bearing 0-layer alterations, but it has little effect on the fusion of vacuoles with wild-type SNAREs. HOPS proofreads at two levels, inhibiting the formation of trans-SNARE complexes with altered 0-layers and suppressing the ability of these mismatched 0-layer trans-SNARE complexes to support membrane fusion. HOPS proofreading also extends to other parts of the SNARE complex, because it suppresses the fusion of trans-SNARE complexes formed without the N-terminal Phox homology domain of Vam7p (Q(c)). Unlike some other SM proteins, HOPS proofreading does not require the Vam3p (Q(a)) N-terminal domain. HOPS thus proofreads SNARE domain and N-terminal domain structures and regulates the fusion capacity of trans-SNARE complexes, only allowing full function for wild-type SNARE configurations. This is the most direct evidence to date that HOPS is directly involved in the fusion event.

Reference Type
Journal Article | Research Support, N.I.H., Extramural
Authors
Starai VJ, Hickey CM, Wickner W
Primary Lit For
VAM6 | VPS41 | PEP3 | PEP5 | NYV1 | VAM3 | VPS16 | VPS33 | HOPS tethering complex
Additional Lit For
SEC17 | VAM7 | VTI1

Gene Ontology Annotations 6 entries for 6 genes


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Gene/ComplexQualifierGene Ontology TermAnnotation ExtensionEvidenceSourceAssigned On
VAM6involved inregulation of SNARE complex assemblyIDASGD2013-08-07
VPS41involved inregulation of SNARE complex assemblyIDASGD2013-08-07
PEP3involved inregulation of SNARE complex assemblyIDASGD2013-08-07
VPS33involved inregulation of SNARE complex assemblyIDASGD2013-08-07
PEP5involved inregulation of SNARE complex assemblyIDASGD2013-08-07
VPS16involved inregulation of SNARE complex assemblyIDASGD2013-08-07
Showing 1 to 6 of 6 entries

Interaction Annotations


Genetic Interactions

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Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions 5 entries for 6 genes

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InteractorInteractorAssayAnnotationActionModification
PEP3VPS33Reconstituted Complexmanually curatedHit-BaitNo Modification
VAM6VPS33Reconstituted Complexmanually curatedHit-BaitNo Modification
VPS33PEP5Reconstituted Complexmanually curatedBait-HitNo Modification
VPS33VPS16Reconstituted Complexmanually curatedBait-HitNo Modification
VPS41VPS33Reconstituted Complexmanually curatedHit-BaitNo Modification
Showing 1 to 5 of 5 entries