7ZLJ

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

7ZLJ の概要

• エントリーDOI: 10.2210/pdb7zlj/pdb
• EMDBエントリー: 14782
• 分子名称: CMT2-Fab heavy chain, Anti-Fab nanobody, CMT2-Fab light chain, ... (7 entities in total)
• 機能のキーワード: c-mannosyltransferase, membrane protein
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 143945.38

構造登録者

Bloch, J.S.,Mao, R.,Mukherjee, S.,Boilevin, J.,Irobalieva, R.,Darbre, T.,Reymond, J.L.,Kossiakoff, A.A.,Goddard-Borger, E.D.,Locher, K.P. (登録日: 2022-04-15, 公開日: 2023-01-11, 最終更新日: 2025-07-09)

主引用文献

Bloch, J.S.,John, A.,Mao, R.,Mukherjee, S.,Boilevin, J.,Irobalieva, R.N.,Darbre, T.,Scott, N.E.,Reymond, J.L.,Kossiakoff, A.A.,Goddard-Borger, E.D.,Locher, K.P.
Structure, sequon recognition and mechanism of tryptophan C-mannosyltransferase.
Nat.Chem.Biol., 19:575-584, 2023

PubMed Abstract: 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.

PubMed: 36604564
DOI: 10.1038/s41589-022-01219-9

実験手法

ELECTRON MICROSCOPY (3.63 Å)