9FYQ

Cryo-EM structure of native SV2A in complex with TeNT-Hc, gangliosides and Pro-Macrobody 5

これはPDB形式変換不可エントリーです。

9FYQ の概要

• エントリーDOI: 10.2210/pdb9fyq/pdb
• EMDBエントリー: 50889 50891
• 分子名称: Synaptic vesicle glycoprotein 2A, Tetanus toxin heavy chain, Pro-Macrobody 5,Maltose/maltodextrin-binding periplasmic protein, ... (8 entities in total)
• 機能のキーワード: synaptic vesicles, mfs transporter, neurotransmission, clostridial neurotoxins, membrane protein
• 由来する生物種: Clostridium tetani E88; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 195375.64

構造登録者

Schenck, S.,Brunner, J.D. (登録日: 2024-07-03, 公開日: 2025-05-21, 最終更新日: 2025-07-09)

主引用文献

Schenck, S.,Laeremans, T.,Steyaert, J.,Brunner, J.D.
Structures of native SV2A reveal the binding mode for tetanus neurotoxin and anti-epileptic racetams.
Nat Commun, 16:4172-4172, 2025

PubMed Abstract: The synaptic vesicle glycoprotein 2A (SV2A) is a synaptic vesicle (SV) resident with homology to the major facilitator superfamily (MFS) and essential in vertebrate neurotransmission. Despite its unclear physiological role, SV2A is of high medical relevance as it is the target of the anti-epileptic drug Levetiracetam (LEV) and a receptor for clostridial neurotoxins (CNTs), among them presumably tetanus neurotoxin (TeNT). To obtain detailed insights about these molecular interactions we subjected native SV2A, purified from brain tissue, to cryo-EM. We discover that TeNT binds SV2A strikingly different from botulinum neurotoxin A and unveil the precise geometry of TeNT binding to dipartite SV2-ganglioside receptors. The structures deliver compelling support for SV2A as the protein receptor for TeNT in central neurons and reinforce the concepts of the dual receptor hypothesis for CNT entry into neurons. Further, our LEV-bound structure of SV2A reveals the drug-interacting residues, delineates a putative substrate pocket in SV2A and provides insights into the SV2-isoform-specificity of LEV. Our work has implications for CNT engineering from a hitherto unrecognized SV2 binding interface and for improved designs of anti-convulsant drugs in epilepsy treatment.

PubMed: 40325068
DOI: 10.1038/s41467-025-59545-0

実験手法

ELECTRON MICROSCOPY (3.25 Å)