8UOA

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

8UOA の概要

• エントリーDOI: 10.2210/pdb8uoa/pdb
• EMDBエントリー: 42432
• 分子名称: Synaptic vesicle glycoprotein 2A, Nanobody, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: synaptic vesicle, slc22, inhibitor, nanobody, transport protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 92493.63

構造登録者

Mittal, A.,Martin, M.F.,Levin, E.,Adams, C.,Yang, M.,Ledecq, M.,Horanyi, P.S.,Coleman, J.A. (登録日: 2023-10-19, 公開日: 2024-05-22, 最終更新日: 2024-11-13)

主引用文献

Mittal, A.,Martin, M.F.,Levin, E.J.,Adams, C.,Yang, M.,Provins, L.,Hall, A.,Procter, M.,Ledecq, M.,Hillisch, A.,Wolff, C.,Gillard, M.,Horanyi, P.S.,Coleman, J.A.
Structures of synaptic vesicle protein 2A and 2B bound to anticonvulsants.
Nat.Struct.Mol.Biol., 2024

PubMed Abstract: 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.

PubMed: 38898101
DOI: 10.1038/s41594-024-01335-1

実験手法

ELECTRON MICROSCOPY (3.8 Å)