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4v11

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Revision as of 01:07, 19 January 2017

Structure of Synaptotagmin-1 with SV2A peptide phosphorylated at Thr84

Structural highlights

4v11 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SYT1_HUMAN] May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone. A Ca(2+)-dependent interaction between synaptotagmin and putative receptors for activated protein kinase C has also been reported. It can bind to at least three additional proteins in a Ca(2+)-independent manner; these are neurexins, syntaxin and AP2. [SV2A_HUMAN] Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily releasable pool of secretory vesicles (By similarity).

Publication Abstract from PubMed

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.

Phosphorylation of Synaptic Vesicle Protein 2A at Thr84 by Casein Kinase 1 Family Kinases Controls the Specific Retrieval of Synaptotagmin-1.,Zhang N, Gordon SL, Fritsch MJ, Esoof N, Campbell DG, Gourlay R, Velupillai S, Macartney T, Peggie M, van Aalten DM, Cousin MA, Alessi DR J Neurosci. 2015 Feb 11;35(6):2492-507. doi: 10.1523/JNEUROSCI.4248-14.2015. PMID:25673844^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zhang N, Gordon SL, Fritsch MJ, Esoof N, Campbell DG, Gourlay R, Velupillai S, Macartney T, Peggie M, van Aalten DM, Cousin MA, Alessi DR. Phosphorylation of Synaptic Vesicle Protein 2A at Thr84 by Casein Kinase 1 Family Kinases Controls the Specific Retrieval of Synaptotagmin-1. J Neurosci. 2015 Feb 11;35(6):2492-507. doi: 10.1523/JNEUROSCI.4248-14.2015. PMID:25673844 doi:http://dx.doi.org/10.1523/JNEUROSCI.4248-14.2015

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4v11"

@@ Line 1: / Line 1: @@
 ==Structure of Synaptotagmin-1 with SV2A peptide phosphorylated at Thr84==
 <StructureSection load='4v11' size='340' side='right' caption='[[4v11]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4v11 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4v11 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4v11 RCSB], [http://www.ebi.ac.uk/pdbsum/4v11 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4v11 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4v11 OCA], [http://pdbe.org/4v11 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4v11 RCSB], [http://www.ebi.ac.uk/pdbsum/4v11 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4v11 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4v11" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4v11

From Proteopedia

Revision as of 01:07, 19 January 2017

Structure of Synaptotagmin-1 with SV2A peptide phosphorylated at Thr84

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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