PDBsum entry 2n1t

Exocytosis

PDB id: 2n1t

Contents

Protein chains

69 a.a.

72 a.a.

77 a.a.

74 a.a.

156 a.a.

PDB id:

2n1t

Name:

Exocytosis

Title:

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

Structure:

Vesicle-associated membrane protein 2. Chain: a. Fragment: unp residues 25-93. Synonym: vamp-2, synaptobrevin-2. Engineered: yes. Syntaxin-1a. Chain: b. Fragment: unp residues 188-259. Synonym: neuron-specific antigen hpc-1, synaptotagmin-associated 35

Source:

Rattus norvegicus. Brown rat,rat,rats. Organism_taxid: 10116. Gene: syb2, vamp2. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: sap, stx1a. Homo sapiens. Human.

NMR struc:

5 models

Authors:

K.Brewer,T.Bacaj,A.Cavalli,C.Camilloni,J.Swarbrick,J.Liu,A.Zhou, P.Zhou,N.Barlow,J.Xu,A.Seven,E.Prinslow,R.Voleti,D.Haussinger, A.Bonvin,D.Tomchick,M.Vendruscolo,B.Graham,T.Sudhof,J.Rizo

Key ref:

K.D.Brewer et al. (2015). Dynamic binding mode of a Synaptotagmin-1-SNARE complex in solution. Nat Struct Biol, 22, 555-564. PubMed id: 26030874 DOI: 10.1038/nsmb.3035

Date:

21-Apr-15 Release date: 03-Jun-15

Protein chain

P63045  (VAMP2_RAT) -  Vesicle-associated membrane protein 2 from Rattus norvegicus

Seq: 116 a.a.

Struc: 69 a.a.

Protein chain

P32851  (STX1A_RAT) -  Syntaxin-1A from Rattus norvegicus

Seq: 288 a.a.

Struc: 72 a.a.

Protein chain

P60880  (SNP25_HUMAN) -  Synaptosomal-associated protein 25 from Homo sapiens

Seq: 206 a.a.

Struc: 77 a.a.*

Protein chain

P60880  (SNP25_HUMAN) -  Synaptosomal-associated protein 25 from Homo sapiens

Seq: 206 a.a.

Struc: 74 a.a.

Protein chain

P21579  (SYT1_HUMAN) -  Synaptotagmin-1 from Homo sapiens

Seq: 422 a.a.

Struc: 156 a.a.*

* PDB and UniProt seqs differ at 14 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E: E.C.?

DOI no: 10.1038/nsmb.3035

Nat Struct Biol 22:555-564 (2015)

PubMed id: 26030874

Dynamic binding mode of a Synaptotagmin-1-SNARE complex in solution.

K.D.Brewer, T.Bacaj, A.Cavalli, C.Camilloni, J.D.Swarbrick, J.Liu, A.Zhou, P.Zhou, N.Barlow, J.Xu, A.B.Seven, E.A.Prinslow, R.Voleti, D.Häussinger, A.M.Bonvin, D.R.Tomchick, M.Vendruscolo, B.Graham, T.C.Südhof, J.Rizo.

ABSTRACT

Rapid neurotransmitter release depends on the Ca(2+) 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.