Cryo-EM structure of the human concentrative nucleoside transporter CNT3
Cryo-EM structure of the human concentrative nucleoside transporter CNT3
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人类浓缩核苷转运蛋白 CNT3 的冷冻电镜结构
DOI：
10.1371/journal.pbio.3000790
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发表时间：
2020
期刊：
影响因子：
9.8
通讯作者：
D. Deng
中科院分区：
文献类型：
--
作者：
Yanxia Zhou;Lianghua Liao;Chen Wang;Jialu Li;Pengliang Chi;Q. Xiao;Qingting Liu;Li Guo;Linfeng Sun;D. Deng
浓缩核苷转运体（CNTs）是溶质载体（SLC） 28转运体家族的成员，可促进核苷和治疗性核苷衍生物在质膜上的回收。尽管经过数十年的研究，人体碳纳米管的结构仍然未知。我们确定了人类碳纳米管（hCNT） 3的低温电镜（cro - em）结构，总分辨率为3.6 Å。与其细菌同源物一样，hCNT3呈现三聚体结构，具有额外的n端跨膜螺旋以稳定保守的中心结构域。底物和钠离子的保守结合位点揭示了核苷的选择性转运和独特的偶联机制。hCNT3与细菌同源物的结构比较表明，hCNT3稳定在一个内向的构象中。这项研究为hCNTs的转运机制提供了分子决定因素，并可能促进核苷类药物的设计。
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.
人类浓缩核苷转运蛋白 3 (hCNT3、SLC28A3) 形成环状同源三聚体。
影响因子：
2.9
作者：
Stecula,Adrian;Schlessinger,Avner;Giacomini,KathleenM;Sali,Andrej
通讯作者：
Sali,Andrej