- EMDB-26486: 70S ribosome complex in an intermediate state of translocation bo... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-26486
タイトル
70S ribosome complex in an intermediate state of translocation bound to EF-G(GDP) stalled by Argyrin B
マップデータ
Refine3D (Relion 4.0), re-sampled after pixel calibration
試料
複合体: 70S ribosome in an intermediate state of translocation bound to EF-G(GDP) and ArgyrinB
複合体: 30S ribosomal subunit
RNA: x 1種
タンパク質・ペプチド: x 20種
複合体: 50S ribosomal subunit
RNA: x 2種
タンパク質・ペプチド: x 32種
RNA: x 3種
タンパク質・ペプチド: x 2種
リガンド: x 7種
キーワード
Translocation / EF-G / Argyrin / Ribosome
機能・相同性
機能・相同性情報
ribosome disassembly / guanosine tetraphosphate binding / negative regulation of cytoplasmic translational initiation / stringent response / misfolded RNA binding / translational elongation / Group I intron splicing / RNA folding / translation elongation factor activity / positive regulation of ribosome biogenesis ...ribosome disassembly / guanosine tetraphosphate binding / negative regulation of cytoplasmic translational initiation / stringent response / misfolded RNA binding / translational elongation / Group I intron splicing / RNA folding / translation elongation factor activity / positive regulation of ribosome biogenesis / translational termination / DnaA-L2 complex / negative regulation of translational initiation / negative regulation of DNA-templated DNA replication initiation / mRNA regulatory element binding translation repressor activity / positive regulation of RNA splicing / cytosolic ribosome assembly / ribosome assembly / assembly of large subunit precursor of preribosome / transcription antitermination / translational initiation / regulation of cell growth / DNA-templated transcription termination / maintenance of translational fidelity / mRNA 5'-UTR binding / regulation of translation / large ribosomal subunit / ribosomal small subunit assembly / transferase activity / ribosome binding / ribosomal small subunit biogenesis / 5S rRNA binding / small ribosomal subunit / ribosomal large subunit assembly / small ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / cytoplasmic translation / tRNA binding / negative regulation of translation / rRNA binding / structural constituent of ribosome / ribosome / translation / ribonucleoprotein complex / response to antibiotic / mRNA binding / GTPase activity / GTP binding / RNA binding / zinc ion binding / membrane / cytoplasm / cytosol 類似検索 - 分子機能
Translation elongation factor EFG/EF2 / : / Elongation factor G, domain III / EFG, domain V / Ribosomal protein L1, bacterial-type / Elongation Factor G, domain II / Elongation Factor G, domain III / Ribosomal protein L10, eubacterial, conserved site / Ribosomal protein L10 signature. / Ribosomal protein L10 ...Translation elongation factor EFG/EF2 / : / Elongation factor G, domain III / EFG, domain V / Ribosomal protein L1, bacterial-type / Elongation Factor G, domain II / Elongation Factor G, domain III / Ribosomal protein L10, eubacterial, conserved site / Ribosomal protein L10 signature. / Ribosomal protein L10 / Translation elongation factor EFG/EF2, domain IV / Elongation factor G, domain IV / Elongation factor G, domain IV / Elongation factor G C-terminus / Elongation factor EFG, domain V-like / Elongation factor G C-terminus / EF-G domain III/V-like / Tr-type G domain, conserved site / Translational (tr)-type guanine nucleotide-binding (G) domain signature. / : / Ribosomal protein L1, conserved site / Ribosomal protein L1 signature. / Ribosomal protein L1 / Ribosomal protein L1, 3-layer alpha/beta-sandwich / Translation elongation factor EFTu-like, domain 2 / Ribosomal protein L1-like / Ribosomal protein L1/ribosomal biogenesis protein / Ribosomal protein L1p/L10e family / Ribosomal protein L11, bacterial-type / Ribosomal protein S21, conserved site / Elongation factor Tu domain 2 / Ribosomal protein S21 signature. / Ribosomal protein L25, short-form / Ribosomal protein S14, bacterial/plastid / Ribosomal protein L31 type A / Translational (tr)-type GTP-binding domain / Elongation factor Tu GTP binding domain / Translational (tr)-type guanine nucleotide-binding (G) domain profile. / Ribosomal protein S21 superfamily / Ribosomal protein S16, conserved site / Ribosomal protein S16 signature. / Ribosomal protein S21 / Ribosomal protein L31 signature. / Ribosomal protein L31 / Ribosomal protein L31 superfamily / Ribosomal protein L31 / Ribosomal protein S21 / Ribosomal protein L11, conserved site / Ribosomal protein L11 signature. / Ribosomal protein L10-like domain superfamily / Ribosomal protein L10P / Ribosomal protein L10 / Ribosomal protein L16 signature 1. / Ribosomal protein L9 signature. / Ribosomal protein L6, conserved site / Ribosomal protein L6 signature 1. / Ribosomal protein L21, conserved site / Ribosomal protein L21 signature. / Ribosomal protein L9, bacteria/chloroplast / Ribosomal protein L9, C-terminal / Ribosomal protein L9, C-terminal domain / : / Ribosomal protein L9, C-terminal domain superfamily / Ribosomal protein L16 signature 2. / Ribosomal protein L16, conserved site / Ribosomal protein L11, N-terminal / Ribosomal protein L11, N-terminal domain / Ribosomal protein L17 signature. / Ribosomal protein L11/L12 / Ribosomal protein L11, C-terminal / Ribosomal protein L11, C-terminal domain superfamily / Ribosomal protein L11/L12, N-terminal domain superfamily / Ribosomal protein L11/L12 / Ribosomal protein L11, RNA binding domain / Ribosomal L25p family / Ribosomal protein L25 / Ribosomal protein L36 signature. / Ribosomal protein L25/Gln-tRNA synthetase, N-terminal / Ribosomal protein L25/Gln-tRNA synthetase, anti-codon-binding domain superfamily / Ribosomal protein L28/L24 superfamily / Ribosomal protein L33, conserved site / Ribosomal protein L33 signature. / Ribosomal protein L32p, bacterial type / Ribosomal protein L35, conserved site / Ribosomal protein L35 signature. / Ribosomal protein L9 / Ribosomal protein L9, N-terminal domain superfamily / Ribosomal protein L9, N-terminal / Ribosomal protein L9, N-terminal domain / Ribosomal protein L28 / Ribosomal protein L35, non-mitochondrial / Ribosomal protein L18, bacterial-type / Ribosomal protein S6, conserved site / Ribosomal protein S6 signature. / Ribosomal protein S3, bacterial-type / : / Ribosomal protein S13, bacterial-type / Ribosomal protein S19, bacterial-type / Ribosomal protein L6, bacterial-type / Ribosomal protein S7, bacterial/organellar-type 類似検索 - ドメイン・相同性
Large ribosomal subunit protein uL15 / Small ribosomal subunit protein bS18 / Large ribosomal subunit protein bL36 / Small ribosomal subunit protein bS21 / Large ribosomal subunit protein bL28 / Large ribosomal subunit protein uL24 / Large ribosomal subunit protein bL17 / 30S ribosomal protein S9 / Small ribosomal subunit protein uS13 / 30S ribosomal protein S17 ...Large ribosomal subunit protein uL15 / Small ribosomal subunit protein bS18 / Large ribosomal subunit protein bL36 / Small ribosomal subunit protein bS21 / Large ribosomal subunit protein bL28 / Large ribosomal subunit protein uL24 / Large ribosomal subunit protein bL17 / 30S ribosomal protein S9 / Small ribosomal subunit protein uS13 / 30S ribosomal protein S17 / Large ribosomal subunit protein uL5 / Large ribosomal subunit protein uL23 / Large ribosomal subunit protein bL21 / 50S ribosomal protein L6 / Large ribosomal subunit protein bL20 / Small ribosomal subunit protein uS11 / Small ribosomal subunit protein uS3 / Large ribosomal subunit protein bL34 / Small ribosomal subunit protein bS16 / Large ribosomal subunit protein uL1 / Small ribosomal subunit protein bS20 / Large ribosomal subunit protein uL29 / Large ribosomal subunit protein bL25 / Large ribosomal subunit protein bL32 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein uS15 / Large ribosomal subunit protein bL33 / Small ribosomal subunit protein uS2 / 50S ribosomal protein L18 / 50S ribosomal protein L4 / Small ribosomal subunit protein bS6 / Small ribosomal subunit protein uS7 / Elongation factor G / Large ribosomal subunit protein uL10 / Large ribosomal subunit protein uL11 / Large ribosomal subunit protein bL27 / Large ribosomal subunit protein bL31 / Large ribosomal subunit protein bL35 / Small ribosomal subunit protein uS12 / Small ribosomal subunit protein uS4 / Small ribosomal subunit protein uS5 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein uL2 / Large ribosomal subunit protein uL3 / Large ribosomal subunit protein uL22 / Small ribosomal subunit protein uS19 / Large ribosomal subunit protein uL13 / Large ribosomal subunit protein uL14 / Small ribosomal subunit protein uS14 / Large ribosomal subunit protein bL19 / Small ribosomal subunit protein uS10 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein bL9 類似検索 - 構成要素
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM079238
米国
Swedish Research Council
2017-06313
スウェーデン
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM115327-Tan
米国
引用
ジャーナル: Proc Natl Acad Sci U S A / 年: 2022 タイトル: The cyclic octapeptide antibiotic argyrin B inhibits translation by trapping EF-G on the ribosome during translocation. 著者: Maximiliane Wieland / Mikael Holm / Emily J Rundlet / Martino Morici / Timm O Koller / Tinashe P Maviza / Domen Pogorevc / Ilya A Osterman / Rolf Müller / Scott C Blanchard / Daniel N Wilson / 要旨: Argyrins are a family of naturally produced octapeptides that display promising antimicrobial activity against Pseudomonas aeruginosa. Argyrin B (ArgB) has been shown to interact with an elongated ...Argyrins are a family of naturally produced octapeptides that display promising antimicrobial activity against Pseudomonas aeruginosa. Argyrin B (ArgB) has been shown to interact with an elongated form of the translation elongation factor G (EF-G), leading to the suggestion that argyrins inhibit protein synthesis by interfering with EF-G binding to the ribosome. Here, using a combination of cryo-electron microscopy (cryo-EM) and single-molecule fluorescence resonance energy transfer (smFRET), we demonstrate that rather than interfering with ribosome binding, ArgB rapidly and specifically binds EF-G on the ribosome to inhibit intermediate steps of the translocation mechanism. Our data support that ArgB inhibits conformational changes within EF-G after GTP hydrolysis required for translocation and factor dissociation, analogous to the mechanism of fusidic acid, a chemically distinct antibiotic that binds a different region of EF-G. These findings shed light on the mechanism of action of the argyrin-class antibiotics on protein synthesis as well as the nature and importance of rate-limiting, intramolecular conformational events within the EF-G-bound ribosome during late-steps of translocation.