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-Structure paper
タイトル | Structure, sequon recognition and mechanism of tryptophan C-mannosyltransferase. |
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ジャーナル・号・ページ | Nat Chem Biol, Vol. 19, Issue 5, Page 575-584, Year 2023 |
掲載日 | 2023年1月5日 |
著者 | Joël S Bloch / Alan John / Runyu Mao / Somnath Mukherjee / Jérémy Boilevin / Rossitza N Irobalieva / Tamis Darbre / Nichollas E Scott / Jean-Louis Reymond / Anthony A Kossiakoff / Ethan D Goddard-Borger / Kaspar P Locher / |
PubMed 要旨 | C-linked glycosylation is essential for the trafficking, folding and function of secretory and transmembrane proteins involved in cellular communication processes. The tryptophan C- ...C-linked glycosylation is essential for the trafficking, folding and function of secretory and transmembrane proteins involved in cellular communication processes. The tryptophan C-mannosyltransferase (CMT) enzymes that install the modification attach a mannose to the first tryptophan of WxxW/C sequons in nascent polypeptide chains by an unknown mechanism. Here, we report cryogenic-electron microscopy structures of Caenorhabditis elegans CMT in four key states: apo, acceptor peptide-bound, donor-substrate analog-bound and as a trapped ternary complex with both peptide and a donor-substrate mimic bound. The structures indicate how the C-mannosylation sequon is recognized by this CMT and its paralogs, and how sequon binding triggers conformational activation of the donor substrate: a process relevant to all glycosyltransferase C superfamily enzymes. Our structural data further indicate that the CMTs adopt an unprecedented electrophilic aromatic substitution mechanism to enable the C-glycosylation of proteins. These results afford opportunities for understanding human disease and therapeutic targeting of specific CMT paralogs. |
リンク | Nat Chem Biol / PubMed:36604564 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.72 - 3.63 Å |
構造データ | EMDB-14779, PDB-7zlg: EMDB-14780, PDB-7zlh: EMDB-14781, PDB-7zli: EMDB-14782, PDB-7zlj: |
化合物 | ChemComp-HOH: ChemComp-IZY: ChemComp-IZU: |
由来 |
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キーワード | MEMBRANE PROTEIN / C-mannosyltransferase |