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TitleStructural basis for the reaction cycle and transport mechanism of human Na-sulfate cotransporter NaS1 (SLC13A1).
Journal, issue, pagesSci Adv, Vol. 10, Issue 47, Page eado6778, Year 2024
Publish dateNov 22, 2024
AuthorsXudong Chen / Youqi Zhang / Jian Yin / Chang Liu / Min Xie / Yixue Wang / Meiying Chen / Rui Zhang / Xinyi Yuan / De Li / Xiangmei Chen / Xin Gao / Guangyan Cai / Sensen Zhang / Boda Zhou / Maojun Yang /
PubMed AbstractSulfate (SO) is a pivotal inorganic anion with essential roles in mammalian physiology. NaS1, a member of solute carrier 13 family and divalent anion/sodium symporter family, functions as a Na- ...Sulfate (SO) is a pivotal inorganic anion with essential roles in mammalian physiology. NaS1, a member of solute carrier 13 family and divalent anion/sodium symporter family, functions as a Na-sulfate cotransporter, facilitating sulfate (re)absorption across renal proximal tubule and small intestine epithelia. While previous studies have linked several human disorders to mutations in the gene, its transport mechanism remains unclear. Here, we report the cryo-electron microscopy structures of five distinct conformations of the human NaS1 at resolutions of 2.7 to 3.3 angstroms, revealing the substrates recognition mechanism and the conformational change of NaS1 during the Na-sulfate cotransport cycle. Our studies delineate the molecular basis of the detailed dynamic transport cycle of NaS1. These findings advance the current understanding of the Na-sulfate cotransport mechanism, human sulfate (re)absorption, and the implications of disease-associated NaS1 mutations.
External linksSci Adv / PubMed:39576865 / PubMed Central
MethodsEM (single particle)
Resolution2.73 - 3.35 Å
Structure data

38953

8y5u

EMDB-38953, PDB-8y5u:
human NaS1 intermediate state 1
Method: EM (single particle) / Resolution: 3.04 Å

38954

8y5w

EMDB-38954, PDB-8y5w:
human NaS1 intermediate state 2
Method: EM (single particle) / Resolution: 2.73 Å

38955

8y5x

EMDB-38955, PDB-8y5x:
human NaS1 intermediate state 3
Method: EM (single particle) / Resolution: 3.25 Å

38959

8y5y

EMDB-38959, PDB-8y5y:
human NaS1 outward state
Method: EM (single particle) / Resolution: 3.3 Å

38960

8y5z

EMDB-38960, PDB-8y5z:
human NaS1 inward state
Method: EM (single particle) / Resolution: 3.35 Å

Chemicals

ChemComp-NA:
Unknown entry

ChemComp-SO4:
SULFATE ION

Source
  • homo sapiens (human)
KeywordsPROTEIN TRANSPORT / membrane sodium anion transporter / membrane sodium anion transproter

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