8uo9

From Proteopedia

(Difference between revisions)

Current revision

Structure of synaptic vesicle protein 2A in complex with a nanobody

Structural highlights

8uo9 is a 2 chain structure with sequence from Homo sapiens and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.3Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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

Epilepsy is a common neurological disorder characterized by abnormal activity of neuronal networks, leading to seizures. The racetam class of anti-seizure medications bind specifically to a membrane protein found in the synaptic vesicles of neurons called synaptic vesicle protein 2 (SV2) A (SV2A). SV2A belongs to an orphan subfamily of the solute carrier 22 organic ion transporter family that also includes SV2B and SV2C. The molecular basis for how anti-seizure medications act on SV2s remains unknown. Here we report cryo-electron microscopy structures of SV2A and SV2B captured in a luminal-occluded conformation complexed with anticonvulsant ligands. The conformation bound by anticonvulsants resembles an inhibited transporter with closed luminal and intracellular gates. Anticonvulsants bind to a highly conserved central site in SV2s. These structures provide blueprints for future drug design and will facilitate future investigations into the biological function of SV2s.

Structures of synaptic vesicle protein 2A and 2B bound to anticonvulsants.,Mittal A, Martin MF, Levin EJ, Adams C, Yang M, Provins L, Hall A, Procter M, Ledecq M, Hillisch A, Wolff C, Gillard M, Horanyi PS, Coleman JA Nat Struct Mol Biol. 2024 Jun 19. doi: 10.1038/s41594-024-01335-1. PMID:38898101^[1]

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

References

↑ Mittal A, Martin MF, Levin EJ, Adams C, Yang M, Provins L, Hall A, Procter M, Ledecq M, Hillisch A, Wolff C, Gillard M, Horanyi PS, Coleman JA. Structures of synaptic vesicle protein 2A and 2B bound to anticonvulsants. Nat Struct Mol Biol. 2024 Jun 19. PMID:38898101 doi:10.1038/s41594-024-01335-1

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/8uo9"

@@ Line 5: / Line 5: @@
 <table><tr><td colspan='2'>[[8uo9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8UO9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UO9 FirstGlance]. <br>
 </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
-<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PS1:1,2-DIDECANOYL-SN-GLYCERO-3-[PHOSPHO-L-SERINE]'>PS1</scene>, <scene name='pdbligand=X49:(4~{S})-1-[[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]-4-[4,4,4-tris(fluoranyl)butyl]pyrrolidin-2-one'>X49</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PS1:1,2-DIDECANOYL-SN-GLYCERO-3-[PHOSPHO-L-SERINE]'>PS1</scene>, <scene name='pdbligand=X49:(4S)-1-{[(4S)-2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(4,4,4-trifluorobutyl)pyrrolidin-2-one'>X49</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8uo9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8uo9 OCA], [https://pdbe.org/8uo9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8uo9 RCSB], [https://www.ebi.ac.uk/pdbsum/8uo9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8uo9 ProSAT]</span></td></tr>
 </table>

8uo9

From Proteopedia

Current revision

Structure of synaptic vesicle protein 2A in complex with a nanobody

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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