6O0V

Crystal structure of the TIR domain G601P mutant from human SARM1, crystal form 2

6O0V の概要

• エントリーDOI: 10.2210/pdb6o0v/pdb
• 分子名称: Sterile alpha and TIR motif-containing protein 1, CHLORIDE ION, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (4 entities in total)
• 機能のキーワード: axon degeneration, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 65796.67

構造登録者

Horsefield, S.,Burdett, H.,Zhang, X.,Manik, M.K.,Shi, Y.,Chen, J.,Tiancong, Q.,Gilley, J.,Lai, J.,Gu, W.,Rank, M.,Casey, L.,Ericsson, D.J.,Foley, G.,Hughes, R.O.,Bosanac, T.,von Itzstein, M.,Rathjen, J.P.,Nanson, J.D.,Boden, M.,Dry, I.B.,Williams, S.J.,Staskawicz, B.J.,Coleman, M.P.,Ve, T.,Dodds, P.N.,Kobe, B. (登録日: 2019-02-17, 公開日: 2019-09-04, 最終更新日: 2024-03-13)

主引用文献

Horsefield, S.,Burdett, H.,Zhang, X.,Manik, M.K.,Shi, Y.,Chen, J.,Qi, T.,Gilley, J.,Lai, J.S.,Rank, M.X.,Casey, L.W.,Gu, W.,Ericsson, D.J.,Foley, G.,Hughes, R.O.,Bosanac, T.,von Itzstein, M.,Rathjen, J.P.,Nanson, J.D.,Boden, M.,Dry, I.B.,Williams, S.J.,Staskawicz, B.J.,Coleman, M.P.,Ve, T.,Dodds, P.N.,Kobe, B.
NAD+cleavage activity by animal and plant TIR domains in cell death pathways.
Science, 365:793-799, 2019

PubMed Abstract: SARM1 (sterile alpha and TIR motif containing 1) is responsible for depletion of nicotinamide adenine dinucleotide in its oxidized form (NAD) during Wallerian degeneration associated with neuropathies. Plant nucleotide-binding leucine-rich repeat (NLR) immune receptors recognize pathogen effector proteins and trigger localized cell death to restrict pathogen infection. Both processes depend on closely related Toll/interleukin-1 receptor (TIR) domains in these proteins, which, as we show, feature self-association-dependent NAD cleavage activity associated with cell death signaling. We further show that SARM1 SAM (sterile alpha motif) domains form an octamer essential for axon degeneration that contributes to TIR domain enzymatic activity. The crystal structures of ribose and NADP (the oxidized form of nicotinamide adenine dinucleotide phosphate) complexes of SARM1 and plant NLR RUN1 TIR domains, respectively, reveal a conserved substrate binding site. NAD cleavage by TIR domains is therefore a conserved feature of animal and plant cell death signaling pathways.

PubMed: 31439792
DOI: 10.1126/science.aax1911

実験手法

X-RAY DIFFRACTION (2.07 Å)