8GNJ

Human SARM1 bounded with NMN and Nanobody-C6, Conformation 2

8GNJ の概要

• エントリーDOI: 10.2210/pdb8gnj/pdb
• EMDBエントリー: 34162 34166
• 分子名称: NAD(+) hydrolase SARM1, Nanobody-C6, BETA-NICOTINAMIDE RIBOSE MONOPHOSPHATE (3 entities in total)
• 機能のキーワード: nad(+)hydrolase, nmn, nanobody, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 172476.31

構造登録者

Cai, Y.,Zhang, H. (登録日: 2022-08-24, 公開日: 2023-01-18, 最終更新日: 2024-10-16)

主引用文献

Hou, Y.N.,Cai, Y.,Li, W.H.,He, W.M.,Zhao, Z.Y.,Zhu, W.J.,Wang, Q.,Mai, X.,Liu, J.,Lee, H.C.,Stjepanovic, G.,Zhang, H.,Zhao, Y.J.
A conformation-specific nanobody targeting the nicotinamide mononucleotide-activated state of SARM1.
Nat Commun, 13:7898-7898, 2022

PubMed Abstract: Sterile alpha (SAM) and Toll/interleukin-1 receptor (TIR) motif containing 1 (SARM1) is an autoinhibitory NAD-consuming enzyme that is activated by the accumulation of nicotinamide mononucleotide (NMN) during axonal injury. Its activation mechanism is not fully understood. Here, we generate a nanobody, Nb-C6, that specifically recognizes NMN-activated SARM1. Nb-C6 stains only the activated SARM1 in cells stimulated with CZ-48, a permeant mimetic of NMN, and partially activates SARM1 in vitro and in cells. Cryo-EM of NMN/SARM1/Nb-C6 complex shows an octameric structure with ARM domains bending significantly inward and swinging out together with TIR domains. Nb-C6 binds to SAM domain of the activated SARM1 and stabilized its ARM domain. Mass spectrometry analyses indicate that the activated SARM1 in solution is highly dynamic and that the neighboring TIRs form transient dimers via the surface close to one BB loop. We show that Nb-C6 is a valuable tool for studies of SARM1 activation.

PubMed: 36550129
DOI: 10.1038/s41467-022-35581-y

実験手法

ELECTRON MICROSCOPY (3.78 Å)