期刊
FEBS JOURNAL
卷 289, 期 6, 页码 1515-1523出版社
WILEY
DOI: 10.1111/febs.16158
关键词
citrate uptake; DASS family; ITS; membrane transporter structure; SLC13 family
资金
- NIH [R01NS108151, R01GM121994, R01DK099023]
- G. Harold and Leila Y. Mathers Foundation
- TESS Research Foundation
- American Epilepsy Society
- Pfizer Inc.
- American Cancer Society Postdoctoral Fellowship [129844-PF-17-135-01-TBE]
- Department of Defense Horizon Award [W81XWH-16-1-0153]
The DASS family consists of various proteins, with NaCT and LaINDY showing high structural similarity to the VcINDY fold and sharing a similar transport mechanism. Studying different structural states helps in understanding their transport cycle.
The divalent anion sodium symporter (DASS) family contains both sodium-driven anion cotransporters and anion/anion exchangers. The family belongs to a broader ion transporter superfamily (ITS), which comprises 24 families of transporters, including those of AbgT antibiotic efflux transporters. The human proteins in the DASS family play major physiological roles and are drug targets. We recently determined multiple structures of the human sodium-dependent citrate transporter (NaCT) and the succinate/dicarboxylate transporter from Lactobacillus acidophilus (LaINDY). Structures of both proteins show high degrees of structural similarity to the previously determined VcINDY fold. Conservation between these DASS protein structures and those from the AbgT family indicates that the VcINDY fold represents the overall protein structure for the entire ITS. The new structures of NaCT and LaINDY are captured in the inward- or outward-facing conformations, respectively. The domain arrangements in these structures agree with a rigid body elevator-type transport mechanism for substrate translocation across the membrane. Two separate NaCT structures in complex with a substrate or an inhibitor allowed us to explain the inhibition mechanism and propose a detailed classification scheme for grouping disease-causing mutations in the human protein. Structural understanding of multiple kinetic states of DASS proteins is a first step toward the detailed characterization of their entire transport cycle.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据