Open AccessCryo-EM structure of the human concentrative nucleoside transporter CNT3
Author(s) -
Yanxia Zhou,
Lianghuan Liao,
Chen Wang,
Jialu Li,
Pengliang Chi,
Qi Xiao,
Qingting Liu,
Li Guo,
Linfeng Sun,
Dong Deng
Publication year - 2020
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3000790
Subject(s) - nucleoside , biology , transporter , nucleoside analogue , nucleoside transporter , transmembrane domain , biophysics , transmembrane protein , biochemistry , cryo electron microscopy , membrane , gene , receptor
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.