4V11
Structure of Synaptotagmin-1 with SV2A peptide phosphorylated at Thr84
Summary for 4V11
Entry DOI | 10.2210/pdb4v11/pdb |
Descriptor | SYNAPTOTAGMIN-1, SYNAPTIC VESICLE GLYCOPROTEIN 2A, CALCIUM ION, ... (5 entities in total) |
Functional Keywords | signaling protein |
Biological source | HOMO SAPIENS (HUMAN) More |
Cellular location | Cytoplasmic vesicle, secretory vesicle membrane ; Single-pass membrane protein : P21579 Cell junction, synapse : Q7L0J3 |
Total number of polymer chains | 2 |
Total formula weight | 18463.23 |
Authors | 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. (deposition date: 2014-09-22, release date: 2015-02-25, Last modification date: 2024-11-06) |
Primary citation | 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 Cited by 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: 25673844DOI: 10.1523/JNEUROSCI.4248-14.2015 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
Download full validation report