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Structure paper

TitleCryo-EM structure of the human sodium-chloride cotransporter NCC.
Journal, issue, pagesSci Adv, Vol. 8, Issue 45, Page eadd7176, Year 2022
Publish dateNov 11, 2022
AuthorsJing Nan / Yafei Yuan / Xuemei Yang / Ziyang Shan / Huihui Liu / Feiwen Wei / Wei Zhang / Yanqing Zhang /
PubMed AbstractThe sodium-chloride cotransporter NCC mediates the coupled import of sodium and chloride across the plasma membrane, playing vital roles in kidney extracellular fluid volume and blood pressure ...The sodium-chloride cotransporter NCC mediates the coupled import of sodium and chloride across the plasma membrane, playing vital roles in kidney extracellular fluid volume and blood pressure control. Here, we present the full-length structure of human NCC, with 2.9 Å for the transmembrane domain and 3.8 Å for the carboxyl-terminal domain. NCC adopts an inward-open conformation and a domain-swap dimeric assembly. Conserved ion binding sites among the cation-chloride cotransporters and the Na2 site are observed in our structure. A unique His residue in the substrate pocket in NCC potentially interacts with Na1 and Cl1 and might also mediate the coordination of Na2 through a Ser residue. Putative observed water molecules are indicated to participate in the coordination of ions and TM coupling. Together with transport activity assays, our structure provides the first glimpse of NCC and defines ion binding sites, promoting drug development for hypertension targeting on NCC.
External linksSci Adv / PubMed:36351028 / PubMed Central
MethodsEM (single particle)
Resolution2.85 - 3.77 Å
Structure data

33641

7y6i

EMDB-33641, PDB-7y6i:
Cryo-EM structure of human sodium-chloride cotransporter
Method: EM (single particle) / Resolution: 2.85 Å

33803

7yg0

EMDB-33803, PDB-7yg0:
Cryo-EM structure of human sodium-chloride cotransporter
Method: EM (single particle) / Resolution: 3.75 Å

33804

7yg1

EMDB-33804, PDB-7yg1:
Cryo-EM structure of the C-terminal domain of the human sodium-chloride cotransporter
Method: EM (single particle) / Resolution: 3.77 Å

Chemicals

ChemComp-CL:
Unknown entry / Chloride

ChemComp-NA:
Unknown entry

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

ChemComp-LPE:
1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM / POPC

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / transporter / cation-chloride cotransporter

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