26VD

SMVT in the outward-open state

Summary for 26VD

• Entry DOI: 10.2210/pdb26vd/pdb
• EMDB information: 80906
• Descriptor: Sodium-dependent multivitamin transporter (1 entity in total)
• Functional Keywords: sodium-dependent multivitamin transporter, smvt, slc5a6, transport protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 1
• Total formula weight: 68000.70

Authors

Zhang, Z.,Zhen, Q. (deposition date: 2026-05-16, release date: 2026-07-08)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (4.3 Å)