Cryo-EM structure of the sodium-driven chloride/bicarbonate exchanger NDCBE.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 09 2021
28 09 2021
Historique:
received:
09
03
2021
accepted:
08
09
2021
entrez:
29
9
2021
pubmed:
30
9
2021
medline:
31
10
2021
Statut:
epublish
Résumé
SLC4 transporters play significant roles in pH regulation and cellular sodium transport. The previously solved structures of the outward facing (OF) conformation for AE1 (SLC4A1) and NBCe1 (SLC4A4) transporters revealed an identical overall fold despite their different transport modes (chloride/bicarbonate exchange versus sodium-carbonate cotransport). However, the exact mechanism determining the different transport modes in the SLC4 family remains unknown. In this work, we report the cryo-EM 3.4 Å structure of the OF conformation of NDCBE (SLC4A8), which shares transport properties with both AE1 and NBCe1 by mediating the electroneutral exchange of sodium-carbonate with chloride. This structure features a fully resolved extracellular loop 3 and well-defined densities corresponding to sodium and carbonate ions in the tentative substrate binding pocket. Further, we combine computational modeling with functional studies to unravel the molecular determinants involved in NDCBE and SLC4 transport.
Identifiants
pubmed: 34584093
doi: 10.1038/s41467-021-25998-2
pii: 10.1038/s41467-021-25998-2
pmc: PMC8478935
doi:
Substances chimiques
Recombinant Proteins
0
SLC4A8 protein, human
0
Sodium-Bicarbonate Symporters
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
5690Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK077162
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM116961
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR023057
Pays : United States
Organisme : NIGMS NIH HHS
ID : U24 GM116792
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021. The Author(s).
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