 |
PDBsum entry 4v11
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Signaling protein
|
PDB id
|
|
|
|
4v11
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Signaling protein
|
|
|
Title:
|
|
Structure of synaptotagmin-1 with sv2a peptide phosphorylated at thr84
|
|
Structure:
|
|
Synaptotagmin-1. Chain: a. Fragment: c2b domain, unp residues 273-422. Synonym: synaptotagmin i, syti, p65. Engineered: yes. Synaptic vesicle glycoprotein 2a. Chain: b. Fragment: unp residues 81-90. Synonym: sv2a.
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Organism_taxid: 9606
|
|
Resolution:
|
|
|
1.95Å
|
R-factor:
|
0.153
|
R-free:
|
0.196
|
|
|
Authors:
|
|
N.Zhang,S.L.Gordon,M.J.Fritsch,N.Esoof,D.Campbell,R.Gourlay, S.Velupillai,T.Macartney,M.Peggie,D.M.F.Vanaalten,M.A.Cousin, D.R.Alessi
|
|
Key ref:
|
|
N.Zhang
et al.
(2015).
Phosphorylation of synaptic vesicle protein 2A at Thr84 by casein kinase 1 family kinases controls the specific retrieval of synaptotagmin-1.
J Neurosci,
35,
2492-2507.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
22-Sep-14
|
Release date:
|
25-Feb-15
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
P21579
(SYT1_HUMAN) -
Synaptotagmin-1 from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
422 a.a.
150 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
J Neurosci
35:2492-2507
(2015)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Phosphorylation of synaptic vesicle protein 2A at Thr84 by casein kinase 1 family kinases controls the specific retrieval of synaptotagmin-1.
|
|
N.Zhang,
S.L.Gordon,
M.J.Fritsch,
N.Esoof,
D.G.Campbell,
R.Gourlay,
S.Velupillai,
T.Macartney,
M.Peggie,
D.M.van Aalten,
M.A.Cousin,
D.R.Alessi.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Synaptic vesicle protein 2A (SV2A) is a ubiquitous component of synaptic
vesicles (SVs). It has roles in both SV trafficking and neurotransmitter
release. We demonstrate that Casein kinase 1 family members, including isoforms
of Tau-tubulin protein kinases (TTBK1 and TTBK2), phosphorylate human SV2A at
two constellations of residues, namely Cluster-1 (Ser42, Ser45, and Ser47) and
Cluster-2 (Ser80, Ser81, and Thr84). These residues are also phosphorylated in
vivo, and the phosphorylation of Thr84 within Cluster-2 is essential for
triggering binding to the C2B domain of human synaptotagmin-1. We show by
crystallographic and other analyses that the phosphorylated Thr84 residue binds
to a pocket formed by three conserved Lys residues (Lys314, Lys326, and Lys328)
on the surface of the synaptotagmin-1 C2B domain. Finally, we observed
dysfunctional synaptotagmin-1 retrieval during SV endocytosis by ablating its
phospho-dependent interaction with SV2A, knockdown of SV2A, or rescue with a
phosphorylation-null Thr84 SV2A mutant in primary cultures of mouse neurons.
This study reveals fundamental details of how phosphorylation of Thr84 on SV2A
controls its interaction with synaptotagmin-1 and implicates SV2A as a
phospho-dependent chaperone required for the specific retrieval of
synaptotagmin-1 during SV endocytosis.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Links
