5NQA

Crystal structure of GalNAc-T4 in complex with the monoglycopeptide 3

5NQA の概要

• エントリーDOI: 10.2210/pdb5nqa/pdb
• 分子名称: Polypeptide N-acetylgalactosaminyltransferase 4, Monoglycopeptide 3, 1,2-ETHANEDIOL, ... (6 entities in total)
• 機能のキーワード: galnac-t4, galnac-t2, chimeras, glycosylation preferences, std-nmr, flexible linker, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Golgi apparatus membrane ; Single-pass type II membrane protein : Q8N4A0
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 140480.98

構造登録者

de las Rivas, M.,Lira-Navarrete, E.,Daniel, E.J.P.,Companon, I.,Coelho, H.,Diniz, A.,Jimenez-Barbero, J.,Peregrina, J.M.,Clausen, H.,Corzana, F.,Marcelo, F.,Jimenez-Oses, G.,Gerken, T.A.,Hurtado-Guerrero, R. (登録日: 2017-04-19, 公開日: 2017-12-20, 最終更新日: 2024-10-16)

主引用文献

Rivas, M.L.,Lira-Navarrete, E.,Daniel, E.J.P.,Companon, I.,Coelho, H.,Diniz, A.,Jimenez-Barbero, J.,Peregrina, J.M.,Clausen, H.,Corzana, F.,Marcelo, F.,Jimenez-Oses, G.,Gerken, T.A.,Hurtado-Guerrero, R.
The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences.
Nat Commun, 8:1959-1959, 2017

PubMed Abstract: The polypeptide GalNAc-transferases (GalNAc-Ts), that initiate mucin-type O-glycosylation, consist of a catalytic and a lectin domain connected by a flexible linker. In addition to recognizing polypeptide sequence, the GalNAc-Ts exhibit unique long-range N- and/or C-terminal prior glycosylation (GalNAc-O-Ser/Thr) preferences modulated by the lectin domain. Here we report studies on GalNAc-T4 that reveal the origins of its unique N-terminal long-range glycopeptide specificity, which is the opposite of GalNAc-T2. The GalNAc-T4 structure bound to a monoglycopeptide shows that the GalNAc-binding site of its lectin domain is rotated relative to the homologous GalNAc-T2 structure, explaining their different long-range preferences. Kinetics and molecular dynamics simulations on several GalNAc-T2 flexible linker constructs show altered remote prior glycosylation preferences, confirming that the flexible linker dictates the rotation of the lectin domain, thus modulating the GalNAc-Ts' long-range preferences. This work for the first time provides the structural basis for the different remote prior glycosylation preferences of the GalNAc-Ts.

PubMed: 29208955
DOI: 10.1038/s41467-017-02006-0

実験手法

X-RAY DIFFRACTION (1.9 Å)