26VB

D-pantothenic acid-bound SMVT in the occluded state

26VB の概要

• エントリーDOI: 10.2210/pdb26vb/pdb
• EMDBエントリー: 80904
• 分子名称: Sodium-dependent multivitamin transporter, PANTOTHENOIC ACID (2 entities in total)
• 機能のキーワード: sodium-dependent multivitamin transporter, smvt, slc5a6, d-pantothenic acid, transport protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 68219.94

構造登録者

Zhang, Z.,Zhen, Q. (登録日: 2026-05-16, 公開日: 2026-07-08)

主引用文献

Zhen, Q.,Wang, M.,Zhang, Z.
Structural basis for multivitamin recognition and transport by human SMVT.
Nat Commun, 2026

PubMed Abstract: The human sodium-dependent multivitamin transporter (SMVT, SLC5A6) mediates cellular uptake of essential metabolic cofactors, including biotin, pantothenate, and lipoate. Its dysfunction is associated with neurological disorders, metabolic abnormalities, and cancer. However, the molecular mechanism underlying its multi-substrate transport has remained elusive. Here, we present cryo-electron microscopy structures of human SMVT in three conformational states: occluded, outward-open, and inward-open. These structural snapshots capture the complete transport cycle and reveal a conserved substrate-binding pocket near a kinked transmembrane helix (TM1). Within this pocket, substrate carboxyl groups are electrostatically anchored, while distinct chemical moieties interact with specific polar and hydrophobic residues. Functional assays identify key binding residues and elucidate the pathogenic effects of disease-associated mutations. Further structural analysis delineates the principles of substrate discrimination within the SLC5 transporter family. Together, our work provides a structural framework for SMVT's polyspecificity and lays a foundation for understanding related diseases and developing targeted therapeutic strategies.

PubMed: 42364996
DOI: 10.1038/s41467-026-74948-3

実験手法

ELECTRON MICROSCOPY (3.7 Å)