[English] 日本語
Yorodumi Papers
- Database of articles cited by EMDB/PDB/SASBDB data -

+
Search query

Keywords
Structure methods
Author
Journal
IF

-
Structure paper

TitleMechanism of anion exchange and small-molecule inhibition of pendrin.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 346, Year 2024
Publish dateJan 6, 2024
AuthorsLie Wang / Anthony Hoang / Eva Gil-Iturbe / Arthur Laganowsky / Matthias Quick / Ming Zhou /
PubMed AbstractPendrin (SLC26A4) is an anion exchanger that mediates bicarbonate (HCO) exchange for chloride (Cl) and is crucial for maintaining pH and salt homeostasis in the kidney, lung, and cochlea. Pendrin ...Pendrin (SLC26A4) is an anion exchanger that mediates bicarbonate (HCO) exchange for chloride (Cl) and is crucial for maintaining pH and salt homeostasis in the kidney, lung, and cochlea. Pendrin also exports iodide (I) in the thyroid gland. Pendrin mutations in humans lead to Pendred syndrome, causing hearing loss and goiter. Inhibition of pendrin is a validated approach for attenuating airway hyperresponsiveness in asthma and for treating hypertension. However, the mechanism of anion exchange and its inhibition by drugs remains poorly understood. We applied cryo-electron microscopy to determine structures of pendrin from Sus scrofa in the presence of either Cl, I, HCO or in the apo-state. The structures reveal two anion-binding sites in each protomer, and functional analyses show both sites are involved in anion exchange. The structures also show interactions between the Sulfate Transporter and Anti-Sigma factor antagonist (STAS) and transmembrane domains, and mutational studies suggest a regulatory role. We also determine the structure of pendrin in a complex with niflumic acid (NFA), which uncovers a mechanism of inhibition by competing with anion binding and impeding the structural changes necessary for anion exchange. These results reveal directions for understanding the mechanisms of anion selectivity and exchange and their regulations by the STAS domain. This work also establishes a foundation for analyzing the pathophysiology of mutations associated with Pendred syndrome.
External linksNat Commun / PubMed:38184688 / PubMed Central
MethodsEM (single particle)
Resolution2.5 - 3.0 Å
Structure data

40470

8sgw

EMDB-40470, PDB-8sgw:
Pendrin in complex with chloride
Method: EM (single particle) / Resolution: 2.5 Å

40479

8sh3

EMDB-40479, PDB-8sh3:
Pendrin in complex with iodide
Method: EM (single particle) / Resolution: 2.8 Å

40483

8shc

EMDB-40483, PDB-8shc:
Pendrin in complex with Niflumic acid
Method: EM (single particle) / Resolution: 3.0 Å

40507

8sie

EMDB-40507, PDB-8sie:
Pendrin in complex with bicarbonate
Method: EM (single particle) / Resolution: 2.7 Å

42588

8uuk

EMDB-42588, PDB-8uuk:
Pendrin in apo
Method: EM (single particle) / Resolution: 2.5 Å

Chemicals

ChemComp-CLR:
CHOLESTEROL

ChemComp-LBN:
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine / phospholipid*YM

ChemComp-CL:
Unknown entry

ChemComp-DMU:
DECYL-BETA-D-MALTOPYRANOSIDE / detergent*YM

ChemComp-AV0:
Lauryl Maltose Neopentyl Glycol

ChemComp-IOD:
IODIDE ION

ChemComp-NFL:
2-{[3-(TRIFLUOROMETHYL)PHENYL]AMINO}NICOTINIC ACID / inhibitor*YM

ChemComp-BCT:
BICARBONATE ION / pH buffer*YM

Source
  • sus scrofa (pig)
KeywordsTRANSPORT PROTEIN / chloride transport / iodide transport / bicarbonate transport

+
About Yorodumi Papers

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi Papers

Database of articles cited by EMDB/PDB/SASBDB data

  • Database of articles cited by EMDB, PDB, and SASBDB entries
  • Using PubMed data

Related info.:EMDB / PDB / SASBDB / Yorodumi / EMN Papers / Changes in new EM Navigator and Yorodumi

Read more