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-基本情報
登録情報 | データベース: PDB / ID: 8p2l | ||||||||||||
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タイトル | A CHIMERA construct containing human SARM1 ARM and SAM domains and C. elegans TIR domain. | ||||||||||||
要素 | NAD(+) hydrolase SARM1,NAD(+) hydrolase tir-1 | ||||||||||||
キーワード | HYDROLASE (加水分解酵素) / SARM1 / TIR-1 / C. elegans (カエノラブディティス・エレガンス) / neurodegeneration (神経変性疾患) / cryo-EM (低温電子顕微鏡法) / structural biology (構造生物学) / NAD+ metabolism / axon Wallerian degeneration | ||||||||||||
機能・相同性 | 機能・相同性情報 serotonin biosynthetic process / negative regulation of MyD88-independent toll-like receptor signaling pathway / MyD88-independent TLR4 cascade / Toll Like Receptor 3 (TLR3) Cascade / NAD catabolic process / NAD+ nucleosidase activity / ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase / protein localization to mitochondrion / NADP+ nucleosidase activity / NAD+ nucleotidase, cyclic ADP-ribose generating ...serotonin biosynthetic process / negative regulation of MyD88-independent toll-like receptor signaling pathway / MyD88-independent TLR4 cascade / Toll Like Receptor 3 (TLR3) Cascade / NAD catabolic process / NAD+ nucleosidase activity / ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase / protein localization to mitochondrion / NADP+ nucleosidase activity / NAD+ nucleotidase, cyclic ADP-ribose generating / nervous system process / cell fate specification / 加水分解酵素; 糖加水分解酵素; N-グリコシル化合物加水分解酵素 / regulation of dendrite morphogenesis / response to axon injury / defense response to fungus / response to glucose / signaling adaptor activity / regulation of neuron apoptotic process / axon cytoplasm / TRAF6-mediated induction of TAK1 complex within TLR4 complex / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / IKK complex recruitment mediated by RIP1 / protein localization / small GTPase binding / cell-cell signaling / cell body / nervous system development / 微小管 / defense response to Gram-negative bacterium / mitochondrial outer membrane / 細胞分化 / defense response to bacterium / 神経繊維 / negative regulation of gene expression / 自然免疫系 / シナプス / 樹状突起 / positive regulation of gene expression / protein kinase binding / シグナル伝達 / positive regulation of transcription by RNA polymerase II / ミトコンドリア / identical protein binding / 細胞質基質 / 細胞質 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) | ||||||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.68 Å | ||||||||||||
データ登録者 | Isupov, M.N. / Opatowsky, Y. | ||||||||||||
資金援助 | イスラエル, 米国, 3件
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引用 | ジャーナル: Cell Rep / 年: 2023 タイトル: Structure-function analysis of ceTIR-1/hSARM1 explains the lack of Wallerian axonal degeneration in C. elegans. 著者: Tami Khazma / Atira Grossman / Julia Guez-Haddad / Chengye Feng / Hadas Dabas / Radhika Sain / Michal Weitman / Ran Zalk / Michail N Isupov / Marc Hammarlund / Michael Hons / Yarden Opatowsky / 要旨: Wallerian axonal degeneration (WD) does not occur in the nematode C. elegans, in contrast to other model animals. However, WD depends on the NADase activity of SARM1, a protein that is also expressed ...Wallerian axonal degeneration (WD) does not occur in the nematode C. elegans, in contrast to other model animals. However, WD depends on the NADase activity of SARM1, a protein that is also expressed in C. elegans (ceSARM/ceTIR-1). We hypothesized that differences in SARM between species might exist and account for the divergence in WD. We first show that expression of the human (h)SARM1, but not ceTIR-1, in C. elegans neurons is sufficient to confer axon degeneration after nerve injury. Next, we determined the cryoelectron microscopy structure of ceTIR-1 and found that, unlike hSARM1, which exists as an auto-inhibited ring octamer, ceTIR-1 forms a readily active 9-mer. Enzymatically, the NADase activity of ceTIR-1 is substantially weaker (10-fold higher Km) than that of hSARM1, and even when fully active, it falls short of consuming all cellular NAD. Our experiments provide insight into the molecular mechanisms and evolution of SARM orthologs and WD across species. | ||||||||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8p2l.cif.gz | 928.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8p2l.ent.gz | 708.7 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8p2l.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/p2/8p2l ftp://data.pdbj.org/pub/pdb/validation_reports/p2/8p2l | HTTPS FTP |
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-関連構造データ
関連構造データ | 17369MC 8p2mC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
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非結晶学的対称性 (NCS) | NCSドメイン:
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