9S6S

Ternary cryo-EM structure of human ALG9 with Dol25-PP-GlcNAc2Man6, Dol25-P-Man and Fab

これはPDB形式変換不可エントリーです。

9S6S の概要

• エントリーDOI: 10.2210/pdb9s6s/pdb
• EMDBエントリー: 54630
• 分子名称: Alpha-1,2-mannosyltransferase ALG9, Hs9-8 Fab heavy chain, Hs9-8 Fab light chain, ... (8 entities in total)
• 機能のキーワード: mannosyltransferase, ternary complex, n-linked glycosylation, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 122635.63

構造登録者

Alexander, J.A.N.,Chen, S.Y.,Mukherjee, S.,de Capitani, M.,Irobalieva, R.N.,Rossi, L.,Agrawal, P.,Kowal, J.,Meirelles, M.A.,Aebi, M.,Reymond, J.L.,Kossiakoff, A.A.,Riniker, S.,Locher, K.P. (登録日: 2025-08-01, 公開日: 2026-03-18, 最終更新日: 2026-04-08)

主引用文献

Alexander, J.A.N.,Chen, S.Y.,Mukherjee, S.,de Capitani, M.,Irobalieva, R.N.,Rossi, L.,Agrawal, P.,Kowal, J.,Meirelles, M.A.,Aebi, M.,Reymond, J.L.,Kossiakoff, A.A.,Riniker, S.,Locher, K.P.
Structures of ALG3/9/12 reveal the assembly logic of the N-glycan oligomannose core.
Nat.Chem.Biol., 2026

PubMed Abstract: Asparagine-linked glycans are essential for the maturation and function of most eukaryotic secretory proteins. The biosynthesis and transfer of dolichylpyrophosphate-anchored GlcNAcManGlc glycan is a highly conserved process occurring in the endoplasmic reticulum (ER) membrane and involving over a dozen membrane proteins whose dysfunction is linked to congenital disorders of glycosylation (CDGs). Three membrane-integral mannosyltransferases, ALG3, ALG9 and ALG12, mediate four consecutive mannosylation reactions that convert GlcNAcMan to GlcNAcMan. Here, using chemoenzymatically synthesized lipid-linked glycan donor and acceptor analogs, we recapitulated this biosynthetic pathway in vitro. High-resolution cryo-electron microscopy structures of pseudo-Michaelis complexes of each step revealed how the branched glycan is accurately synthesized and unwanted side products are averted. Molecular dynamics simulations and mutagenesis studies uncovered a subtle but precise mechanism selecting the dolichylphosphomannose donor substrate over dolichylphosphoglucose, which is also present in the ER membrane. Our results also provide mechanistic explanations for enzyme dysfunction in CDGs and offer opportunities for N-glycan engineering.

PubMed: 41807832
DOI: 10.1038/s41589-026-02164-7

実験手法

ELECTRON MICROSCOPY (2.89 Å)