4V11

Structure of Synaptotagmin-1 with SV2A peptide phosphorylated at Thr84

4V11 の概要

• エントリーDOI: 10.2210/pdb4v11/pdb
• 分子名称: SYNAPTOTAGMIN-1, SYNAPTIC VESICLE GLYCOPROTEIN 2A, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: signaling protein
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Cytoplasmic vesicle, secretory vesicle membrane ; Single-pass membrane protein : P21579; Cell junction, synapse : Q7L0J3
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18463.23

構造登録者

Zhang, N.,Gordon, S.L.,Fritsch, M.J.,Esoof, N.,Campbell, D.,Gourlay, R.,Velupillai, S.,Macartney, T.,Peggie, M.,vanAalten, D.M.F.,Cousin, M.A.,Alessi, D.R. (登録日: 2014-09-22, 公開日: 2015-02-25, 最終更新日: 2024-11-06)

主引用文献

Zhang, N.,Gordon, S.L.,Fritsch, M.J.,Esoof, N.,Campbell, D.G.,Gourlay, R.,Velupillai, S.,Macartney, T.,Peggie, M.,Van Aalten, D.M.F.,Cousin, M.A.,Alessi, D.R.
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-, 2015

PubMed 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.

PubMed: 25673844
DOI: 10.1523/JNEUROSCI.4248-14.2015

実験手法

X-RAY DIFFRACTION (1.95 Å)