Details

Autor(en) / Beteiligte

• Zhou, Yanxia
• Liao, Lianghuan
• Wang, Chen
• Li, Jialu
• Chi, Pengliang
• Xiao, Qingjie
• Liu, Qingting
• Guo, Li
• Sun, Linfeng
• Deng, Dong
• Dutzler, Raimund

Titel

Cryo-EM structure of the human concentrative nucleoside transporter CNT3

Ist Teil von

• PLoS biology, 2020-08, Vol.18 (8), p.e3000790-e3000790

Ort / Verlag

San Francisco: Public Library of Science

Erscheinungsjahr

2020

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Concentrative nucleoside transporters (CNTs), members of the solute carrier (SLC) 28 transporter family, facilitate the salvage of nucleosides and therapeutic nucleoside derivatives across the plasma membrane. Despite decades of investigation, the structures of human CNTs remain unknown. We determined the cryogenic electron microscopy (cryo-EM) structure of human CNT (hCNT) 3 at an overall resolution of 3.6 Å. As with its bacterial homologs, hCNT3 presents a trimeric architecture with additional N-terminal transmembrane helices to stabilize the conserved central domains. The conserved binding sites for the substrate and sodium ions unravel the selective nucleoside transport and distinct coupling mechanism. Structural comparison of hCNT3 with bacterial homologs indicates that hCNT3 is stabilized in an inward-facing conformation. This study provides the molecular determinants for the transport mechanism of hCNTs and potentially facilitates the design of nucleoside drugs.