9OLR

Crystal structure of D59C MelB st bound with alpha-methyl galactoside (aMG)

9OLR の概要

• エントリーDOI: 10.2210/pdb9olr/pdb
• 分子名称: Melibiose permease, methyl alpha-D-galactopyranoside (2 entities in total)
• 機能のキーワード: alpha methyl galactoside, sugar binding, mfs, symporter, membrane protein
• 由来する生物種: Salmonella enterica subsp. enterica serovar Typhimurium
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 54286.68

構造登録者

Guan, L.,Hariharan, P. (登録日: 2025-05-12, 公開日: 2026-02-04, 最終更新日: 2026-02-18)

主引用文献

Hariharan, P.,Shi, Y.,Bakhtiiari, A.,Liang, R.,Viner, R.,Guan, L.
Allosteric effects of the coupling cation in melibiose transporter MelB.
Elife, 14:-, 2026

PubMed Abstract: The major facilitator superfamily (MFS) transporters play significant roles in human health and disease. serovar Typhimurium melibiose permease (MelB) catalyzes the symport of galactosides with Na, H, or Li and is a prototype of MFS transporters. We published the structures of MelB in both inward- and outward-facing conformations, bound to galactoside or Na, and proposed that positive cooperativity of the co-transported solutes is crucial for the symport mechanism. Here, we elucidated the underlying mechanisms by analyzing MelB dynamics and the effects of melibiose, Na, or both using hydrogen-deuterium exchange mass spectrometry (HDX-MS). We also refined the determinants of sugar recognition by solving the crystal structures of a uniporter D59C MelB complexed with melibiose and other sugars, and by identifying a critical water molecule involved in sugar recognition. Our integrated studies, combining structures, HDX-MS, and molecular dynamics simulations, support the conclusion that sugar-binding affinity is directly correlated with protein dynamics. Na acts as an allosteric activator, reducing the flexibility of dynamic residues in the sugar-binding site and in the cytoplasmic gating salt-bridge network, thereby increasing sugar-binding affinity. This study provides a molecular-level framework of the symport mechanism that could serve as a general model for cation-coupled symporters.

PubMed: 41604452
DOI: 10.7554/eLife.108335

実験手法

X-RAY DIFFRACTION (3.68 Å)