2N1T

Dynamic binding mode of a synaptotagmin-1-SNARE complex in solution

Summary for 2N1T

• Entry DOI: 10.2210/pdb2n1t/pdb
• Related: 1SFC 1UOW
• NMR Information: BMRB: 6235
• Descriptor: Vesicle-associated membrane protein 2, Syntaxin-1A, Synaptosomal-associated protein 25, ... (5 entities in total)
• Functional Keywords: synaptotagmin-1, c2b domain, syntaxin-1a, synaptobrevin-2, snap-25, snap-25a, snare complex, exocytosis
• Biological source: Rattus norvegicus (brown rat,rat,rats); More
• Cellular location: Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Single-pass type IV membrane protein: P63045 P32851; Cytoplasm, perinuclear region : P60880 P60880; Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Single-pass membrane protein: P21579
• Total number of polymer chains: 5
• Total formula weight: 51428.32

Authors

Brewer, K.,Bacaj, T.,Cavalli, A.,Camilloni, C.,Swarbrick, J.,Liu, J.,Zhou, A.,Zhou, P.,Barlow, N.,Xu, J.,Seven, A.,Prinslow, E.,Voleti, R.,Haussinger, D.,Bonvin, A.,Tomchick, D.,Vendruscolo, M.,Graham, B.,Sudhof, T.,Rizo, J. (deposition date: 2015-04-21, release date: 2015-06-03, Last modification date: 2024-05-15)

Primary citation

Brewer, K.D.,Bacaj, T.,Cavalli, A.,Camilloni, C.,Swarbrick, J.D.,Liu, J.,Zhou, A.,Zhou, P.,Barlow, N.,Xu, J.,Seven, A.B.,Prinslow, E.A.,Voleti, R.,Haussinger, D.,Bonvin, A.M.,Tomchick, D.R.,Vendruscolo, M.,Graham, B.,Sudhof, T.C.,Rizo, J.
Dynamic binding mode of a Synaptotagmin-1-SNARE complex in solution.
Nat.Struct.Mol.Biol., 22:555-564, 2015

PubMed Abstract: Rapid neurotransmitter release depends on the Ca2+ sensor Synaptotagmin-1 (Syt1) and the SNARE complex formed by synaptobrevin, syntaxin-1 and SNAP-25. How Syt1 triggers release has been unclear, partly because elucidating high-resolution structures of Syt1-SNARE complexes has been challenging. An NMR approach based on lanthanide-induced pseudocontact shifts now reveals a dynamic binding mode in which basic residues in the concave side of the Syt1 C2B-domain β-sandwich interact with a polyacidic region of the SNARE complex formed by syntaxin-1 and SNAP-25. The physiological relevance of this dynamic structural model is supported by mutations in basic residues of Syt1 that markedly impair SNARE-complex binding in vitro and Syt1 function in neurons. Mutations with milder effects on binding have correspondingly milder effects on Syt1 function. Our results support a model whereby dynamic interaction facilitates cooperation between Syt1 and the SNAREs in inducing membrane fusion.

PubMed: 26030874
DOI: 10.1038/nsmb.3035

Experimental method

SOLUTION NMR