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Structure paper

タイトル	Mechanism of cotranslational protein N-myristoylation in human cells.
ジャーナル・号・ページ	Mol Cell, Vol. 85, Issue 14, Page 2749-22758.e8, Year 2025
掲載日	2025年7月17日
著者	Martin Gamerdinger / Blanca Echeverria / Alfred M Lentzsch / Nicolas Burg / Ziyi Fan / Mateusz Jaskolowski / Alain Scaiola / Selina Piening / Shu-Ou Shan / Nenad Ban / Elke Deuerling /
PubMed 要旨	N-myristoyltransferases (NMTs) cotranslationally transfer the fatty acid myristic acid to the N terminus of newly synthesized proteins, regulating their function and cellular localization. These ...N-myristoyltransferases (NMTs) cotranslationally transfer the fatty acid myristic acid to the N terminus of newly synthesized proteins, regulating their function and cellular localization. These enzymes are important drug targets for the treatment of cancer and viral infections. N-myristoylation of nascent proteins occurs specifically on N-terminal glycine residues after the excision of the initiator methionine by methionine aminopeptidases (METAPs). How NMTs interact with ribosomes and gain timely and specific access to their substrates remains unknown. Here, we show that human NMT1 exchanges with METAP1 at the ribosomal tunnel exit to form an active cotranslational complex together with the nascent polypeptide-associated complex (NAC). NMT1 binding is sequence selective and specifically triggered by methionine excision, which exposes the N-myristoylation motif in the nascent chain. The revealed mode of interaction of NMT1 with NAC and the methionine-cleaved nascent protein elucidates how a specific subset of proteins can be efficiently N-myristoylated in human cells.
リンク	Mol Cell / PubMed:40639378
手法	EM (単粒子)
解像度	2.8 - 3.43 Å
構造データ	53295 9qqa EMDB-53295, PDB-9qqa: Ternary complex of translating ribosome, NAC and NMT1 手法: EM (単粒子) / 解像度: 2.8 Å 53296 9qqb EMDB-53296, PDB-9qqb: Quaternary complex of a translating ribosome, NAC, NMT1, and NatA 手法: EM (単粒子) / 解像度: 3.43 Å
化合物	ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-UNX: Unknown entry ChemComp-SPD: SPERMIDINE / スペルミジン ChemComp-SPM: SPERMINE / スペルミン ChemComp-ZN: Unknown entry ChemComp-HOH: WATER ChemComp-IHP: INOSITOL HEXAKISPHOSPHATE / myo-イノシト-ル六りん酸
由来	oryctolagus cuniculus (ウサギ) homo sapiens (ヒト)
キーワード	RIBOSOME / Translation / co-translational protein processing