- EMDB-14782: Cryo-EM structure of C-mannosyltransferase CeDPY19, in ternary co... -
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データベース: EMDB / ID: EMD-14782
タイトル
Cryo-EM structure of C-mannosyltransferase CeDPY19, in ternary complex with Dol25-P-C-Man and acceptor peptide, bound to CMT2-Fab and anti-Fab nanobody
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複合体: C-mannosyltransferase CeDPY19, in ternary complex with Dol25-P-C-Man and acceptor peptide, bound to CMT2-Fab and anti-Fab nanobody
ジャーナル: Nat Chem Biol / 年: 2023 タイトル: Structure, sequon recognition and mechanism of tryptophan C-mannosyltransferase. 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 ...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 / 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.