RGD Reference Report - A conformational switch in complexin is required for synaptotagmin to trigger synaptic fusion. - Rat Genome Database

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A conformational switch in complexin is required for synaptotagmin to trigger synaptic fusion.

Authors: Krishnakumar, Shyam S  Radoff, Daniel T  Kümmel, Daniel  Giraudo, Claudio G  Li, Feng  Khandan, Lavan  Baguley, Stephanie Wood  Coleman, Jeff  Reinisch, Karin M  Pincet, Frederic  Rothman, James E 
Citation: Krishnakumar SS, etal., Nat Struct Mol Biol. 2011 Jul 24;18(8):934-40. doi: 10.1038/nsmb.2103.
RGD ID: 13432226
Pubmed: PMID:21785412   (View Abstract at PubMed)
PMCID: PMC3668341   (View Article at PubMed Central)
DOI: DOI:10.1038/nsmb.2103   (Journal Full-text)

The crystal structure of complexin bound to a prefusion SNAREpin mimetic shows that the accessory helix extends away from the SNAREpin in an 'open' conformation, binding another SNAREpin and inhibiting its assembly, to clamp fusion. In contrast, the accessory helix in the postfusion complex parallels the SNARE complex in a 'closed' conformation. Here we use targeted mutations, FRET spectroscopy and a functional assay that reconstitutes Ca(2+)-triggered exocytosis to show that the conformational switch from open to closed in complexin is needed for synaptotagmin-Ca(2+) to trigger fusion. Triggering fusion requires the zippering of three crucial aspartate residues in the switch region (residues 64-68) of v-SNARE. Conformational switching in complexin is integral to clamp release and is probably triggered when its accessory helix is released from its trans-binding to the neighboring SNAREpin, allowing the v-SNARE to complete zippering and open a fusion pore.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:P60880-213432226PMID:21785412IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Stx1a  (syntaxin 1A)


Additional Information