Conserved structural features of the synaptic fusion complex: SNARE proteins reclassified as Q- and R-SNAREs

AUTOR(ES)

Fasshauer, Dirk

FONTE

The National Academy of Sciences

RESUMO

SNARE [soluble NSF (N-ethylmaleimide-sensitive fusion protein) attachment protein receptor] proteins are essential for membrane fusion and are conserved from yeast to humans. Sequence alignments of the most conserved regions were mapped onto the recently solved crystal structure of the heterotrimeric synaptic fusion complex. The association of the four α-helices in the synaptic fusion complex structure produces highly conserved layers of interacting amino acid side chains in the center of the four-helix bundle. Mutations in these layers reduce complex stability and cause defects in membrane traffic even in distantly related SNAREs. When syntaxin-4 is modeled into the synaptic fusion complex as a replacement of syntaxin-1A, no major steric clashes arise and the most variable amino acids localize to the outer surface of the complex. We conclude that the main structural features of the neuronal complex are highly conserved during evolution. On the basis of these features we have reclassified SNARE proteins into Q-SNAREs and R-SNAREs, and we propose that fusion-competent SNARE complexes generally consist of four-helix bundles composed of three Q-SNAREs and one R-SNARE.

Documentos Relacionados

• Organelle docking: R-SNAREs are late
• Determinants of liposome fusion mediated by synaptic SNARE proteins
• SNARE-complex disassembly by NSF follows synaptic-vesicle fusion
• A SNARE complex mediating fusion of late endosomes defines conserved properties of SNARE structure and function
• Synaptic vesicle membrane fusion complex: action of clostridial neurotoxins on assembly.