- EMDB-26036: Mammalian 80S ribosome bound with the ALS/FTD-associated dipeptid... -
+
データを開く
IDまたはキーワード:
読み込み中...
-
基本情報
登録情報
データベース: EMDB / ID: EMD-26036
タイトル
Mammalian 80S ribosome bound with the ALS/FTD-associated dipeptide repeat protein GR20
マップデータ
Rabbit 80S ribosome with GR20
試料
複合体: Mamalian 80S ribosome bound with the ALS/FTD-associated dipeptide repeat protein GR20
RNA: x 6種
タンパク質・ペプチド: x 78種
リガンド: x 1種
キーワード
Ribosomal binding peptide / ALS/FTD-associated dipeptide repeat protein / RIBOSOME
機能・相同性
機能・相同性情報
ribosomal subunit / exit from mitosis / optic nerve development / retinal ganglion cell axon guidance / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / phagocytic cup / ribosomal small subunit export from nucleus / rough endoplasmic reticulum / translation regulator activity ...ribosomal subunit / exit from mitosis / optic nerve development / retinal ganglion cell axon guidance / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / phagocytic cup / ribosomal small subunit export from nucleus / rough endoplasmic reticulum / translation regulator activity / gastrulation / MDM2/MDM4 family protein binding / cytosolic ribosome / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / positive regulation of apoptotic signaling pathway / maturation of SSU-rRNA / small-subunit processome / spindle / mRNA 5'-UTR binding / antimicrobial humoral immune response mediated by antimicrobial peptide / rRNA processing / rhythmic process / positive regulation of canonical Wnt signaling pathway / regulation of translation / large ribosomal subunit / ribosome binding / ribosomal small subunit biogenesis / ribosomal small subunit assembly / retina development in camera-type eye / small ribosomal subunit / 5S rRNA binding / ribosomal large subunit assembly / cytosolic small ribosomal subunit / large ribosomal subunit rRNA binding / small ribosomal subunit rRNA binding / defense response to Gram-negative bacterium / killing of cells of another organism / perikaryon / cytosolic large ribosomal subunit / cytoplasmic translation / cell differentiation / tRNA binding / mitochondrial inner membrane / postsynaptic density / rRNA binding / ribosome / structural constituent of ribosome / translation / ribonucleoprotein complex / cell division / DNA repair / mRNA binding / apoptotic process / synapse / dendrite / negative regulation of apoptotic process / nucleolus / perinuclear region of cytoplasm / endoplasmic reticulum / Golgi apparatus / DNA binding / RNA binding / zinc ion binding / nucleus / membrane / cytosol / cytoplasm 類似検索 - 分子機能
40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ubiquitin-like protein FUBI / Ribosomal protein L30e / Ribosomal protein L2, archaeal-type / Ribosomal L15/L27a, N-terminal / Ribosomal protein L28e / Ribosomal L28e/Mak16 ...40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ubiquitin-like protein FUBI / Ribosomal protein L30e / Ribosomal protein L2, archaeal-type / Ribosomal L15/L27a, N-terminal / Ribosomal protein L28e / Ribosomal L28e/Mak16 / Ribosomal L28e protein family / metallochaperone-like domain / TRASH domain / : / Ribosomal protein S26e signature. / Ribosomal protein L41 / Ribosomal protein L41 / Ribosomal protein S21e, conserved site / Ribosomal protein S21e signature. / Ribosomal protein S26e / Ribosomal protein S26e superfamily / Ribosomal protein S26e / : / Ribosomal protein S12e signature. / Ribosomal protein S12e / Small (40S) ribosomal subunit Asc1/RACK1 / Ribosomal protein S21e / Ribosomal protein S21e superfamily / Ribosomal protein S21e / Ribosomal protein S2, eukaryotic / S27a-like superfamily / Ribosomal protein L10e, conserved site / Ribosomal protein L10e signature. / Ribosomal protein L27e, conserved site / Ribosomal protein L27e signature. / Ribosomal protein L10e / 40S Ribosomal protein S10 / Ribosomal protein L44e signature. / Plectin/S10, N-terminal / Plectin/S10 domain / Ribosomal protein L24e, conserved site / Ribosomal protein L24e signature. / : / Ribosomal protein S10, eukaryotic/archaeal / Ribosomal protein L19, eukaryotic / Ribosomal protein L19/L19e conserved site / Ribosomal protein L19e signature. / Ribosomal protein L6e signature. / Ribosomal protein S8e subdomain, eukaryotes / Ribosomal protein S25 / S25 ribosomal protein / Ribosomal protein S27a / Ribosomal protein S17e, conserved site / : / Ribosomal protein S27a / Ribosomal protein S17e signature. / Ribosomal protein S27a / Ribosomal protein S3Ae, conserved site / Ribosomal protein S3Ae signature. / Ribosomal protein L44e / Ribosomal protein S30 / Ribosomal protein L44 / Ribosomal protein S30 / Ribosomal protein S2, eukaryotic/archaeal / : / Ribosomal protein L34e, conserved site / Ribosomal protein L34e signature. / Ribosomal protein L5 eukaryotic, C-terminal / Ribosomal L18 C-terminal region / Ribosomal protein L30e signature 1. / 40S ribosomal protein S29/30S ribosomal protein S14 type Z / Ribosomal protein S27e signature. / 40S ribosomal protein S4, C-terminal domain / 40S ribosomal protein S4 C-terminus / Ribosomal protein S4e, N-terminal, conserved site / Ribosomal protein S4e signature. / Ribosomal protein S3, eukaryotic/archaeal / Eukaryotic Ribosomal Protein L27, KOW domain / Ribosomal Protein L6, KOW domain / Ribosomal protein L30e signature 2. / Ribosomal protein L27e / Ribosomal protein S8e, conserved site / Ribosomal protein L27e superfamily / Ribosomal L27e protein family / Ribosomal protein L36e signature. / Ribosomal protein S8e signature. / Ribosomal protein S6, eukaryotic / Ribosomal protein L35Ae, conserved site / Ribosomal protein L30e, conserved site / Ribosomal protein L35Ae signature. / Ribosomal protein L39e, conserved site / Ribosomal protein L39e signature. / 40S ribosomal protein S1/3, eukaryotes / Ribosomal protein S19A/S15e / : / Ribosomal protein L6e / Ribosomal protein L34Ae / Ribosomal protein L34e / Ribosomal protein S17e / Ribosomal protein S17e-like superfamily 類似検索 - ドメイン・相同性
Small ribosomal subunit protein eS32 / Ribosomal protein L36a / Large ribosomal subunit protein uL4 / Large ribosomal subunit protein uL16 / Small ribosomal subunit protein uS4 / Large ribosomal subunit protein uL22 / Large ribosomal subunit protein eL24 / Large ribosomal subunit protein eL33 / Small ribosomal subunit protein eS12 / Large ribosomal subunit protein eL31 ...Small ribosomal subunit protein eS32 / Ribosomal protein L36a / Large ribosomal subunit protein uL4 / Large ribosomal subunit protein uL16 / Small ribosomal subunit protein uS4 / Large ribosomal subunit protein uL22 / Large ribosomal subunit protein eL24 / Large ribosomal subunit protein eL33 / Small ribosomal subunit protein eS12 / Large ribosomal subunit protein eL31 / Large ribosomal subunit protein eL21 / Large ribosomal subunit protein uL29 / Small ribosomal subunit protein uS10 / Small ribosomal subunit protein RACK1 / Ubiquitin-ribosomal protein eS31 fusion protein / Large ribosomal subunit protein eL6 / Large ribosomal subunit protein uL11 / Large ribosomal subunit protein uL15 / Small ribosomal subunit protein uS15 / Large ribosomal subunit protein uL24 / Small ribosomal subunit protein eS1 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein eL43 / Large ribosomal subunit protein uL18 / Small ribosomal subunit protein uS12 / Large ribosomal subunit protein eL15 / 40S ribosomal protein S24 / Large ribosomal subunit protein uL14 / Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein / 40S ribosomal protein S4 / Small ribosomal subunit protein eS25 / Large ribosomal subunit protein eL30 / Small ribosomal subunit protein eS26 / Small ribosomal subunit protein uS7 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein eS28 / 40S ribosomal protein SA / Small ribosomal subunit protein eS8 / Large ribosomal subunit protein uL3 / Small ribosomal subunit protein eS6 / Small ribosomal subunit protein eS21 / Small ribosomal subunit protein uS3 / Small ribosomal subunit protein uS13 / Uncharacterized protein / Small ribosomal subunit protein eS10 / Small ribosomal subunit protein uS17 / Large ribosomal subunit protein uL2 / Large ribosomal subunit protein eL39 / Large ribosomal subunit protein eL36 / Small ribosomal subunit protein eS17 / Large ribosomal subunit protein uL5 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein eL27 / Large ribosomal subunit protein eL34 / Large ribosomal subunit protein eL19 / Small ribosomal subunit protein eS27 / Small ribosomal subunit protein uS19 / Large ribosomal subunit protein eL32 / Small ribosomal subunit protein uS11 / Large ribosomal subunit protein eL28 / Small ribosomal subunit protein uS14 / Large ribosomal subunit protein eL14 / Large ribosomal subunit protein eL37 類似検索 - 構成要素
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM107465
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35GM127094
米国
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
R01NS101986
米国
引用
ジャーナル: Nat Commun / 年: 2022 タイトル: Ribosome inhibition by C9ORF72-ALS/FTD-associated poly-PR and poly-GR proteins revealed by cryo-EM. 著者: Anna B Loveland / Egor Svidritskiy / Denis Susorov / Soojin Lee / Alexander Park / Sarah Zvornicanin / Gabriel Demo / Fen-Biao Gao / Andrei A Korostelev / 要旨: Toxic dipeptide-repeat (DPR) proteins are produced from expanded GC repeats in the C9ORF72 gene, the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ...Toxic dipeptide-repeat (DPR) proteins are produced from expanded GC repeats in the C9ORF72 gene, the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Two DPR proteins, poly-PR and poly-GR, repress cellular translation but the molecular mechanism remains unknown. Here we show that poly-PR and poly-GR of ≥20 repeats inhibit the ribosome's peptidyl-transferase activity at nanomolar concentrations, comparable to specific translation inhibitors. High-resolution cryogenic electron microscopy (cryo-EM) reveals that poly-PR and poly-GR block the polypeptide tunnel of the ribosome, extending into the peptidyl-transferase center (PTC). Consistent with these findings, the macrolide erythromycin, which binds in the tunnel, competes with poly-PR and restores peptidyl-transferase activity. Our results demonstrate that strong and specific binding of poly-PR and poly-GR in the ribosomal tunnel blocks translation, revealing the structural basis of their toxicity in C9ORF72-ALS/FTD.