We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

6rtf

From Proteopedia

Jump to: navigation, search

Structure of murine Solute Carrier 26 family member A9 (Slc26a9) anion transporter in an intermediate state

6rtf, resolution 7.77Å

Structural highlights

6rtf is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 7.77Å
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

S26A9_MOUSE DIDS- and thiosulfate- sensitive anion exchanger mediating chloride, sulfate and oxalate transport (PubMed:15800055, PubMed:17120765). Mediates chloride/bicarbonate exchange or chloride-independent bicarbonate extrusion thus assuring bicarbonate secretion (PubMed:15800055, PubMed:17120765). May prefer chloride anions and mediate uncoupled chloride anion transport in an alternate-access mechanism where a saturable binding site is alternately exposed to either one or the other side of the membrane (PubMed:31339488).^[1] ^[2] ^[3]

Publication Abstract from PubMed

The epithelial anion transporter SLC26A9 contributes to airway surface hydration and gastric acid production. Colocalizing with CFTR, SLC26A9 has been proposed as a target for the treatment of cystic fibrosis. To provide molecular details of its transport mechanism, we present cryo-EM structures and a functional characterization of murine Slc26a9. These structures define the general architecture of eukaryotic SLC26 family members and reveal an unusual mode of oligomerization which relies predominantly on the cytosolic STAS domain. Our data illustrates conformational transitions of Slc26a9, supporting a rapid alternate-access mechanism which mediates uncoupled chloride transport with negligible bicarbonate or sulfate permeability. The characterization of structure-guided mutants illuminates the properties of the ion transport path, including a selective anion binding site located in the center of a mobile module within the transmembrane domain. This study thus provides a structural foundation for the understanding of the entire SLC26 family and potentially facilitates their therapeutic exploitation.

Cryo-EM structures and functional characterization of murine Slc26a9 reveal mechanism of uncoupled chloride transport.,Walter JD, Sawicka M, Dutzler R Elife. 2019 Jul 24;8. pii: 46986. doi: 10.7554/eLife.46986. PMID:31339488^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Xu J, Henriksnas J, Barone S, Witte D, Shull GE, Forte JG, Holm L, Soleimani M. SLC26A9 is expressed in gastric surface epithelial cells, mediates Cl-/HCO3- exchange, and is inhibited by NH4+. Am J Physiol Cell Physiol. 2005 Aug;289(2):C493-505. Epub 2005 Mar 30. PMID:15800055 doi:http://dx.doi.org/00030.2005
↑ Romero MF, Chang MH, Plata C, Zandi-Nejad K, Mercado A, Broumand V, Sussman CR, Mount DB. Physiology of electrogenic SLC26 paralogues. Novartis Found Symp. 2006;273:126-38; discussion 138-47, 261-4 PMID:17120765
↑ Walter JD, Sawicka M, Dutzler R. Cryo-EM structures and functional characterization of murine Slc26a9 reveal mechanism of uncoupled chloride transport. Elife. 2019 Jul 24;8. pii: 46986. doi: 10.7554/eLife.46986. PMID:31339488 doi:http://dx.doi.org/10.7554/eLife.46986
↑ Walter JD, Sawicka M, Dutzler R. Cryo-EM structures and functional characterization of murine Slc26a9 reveal mechanism of uncoupled chloride transport. Elife. 2019 Jul 24;8. pii: 46986. doi: 10.7554/eLife.46986. PMID:31339488 doi:http://dx.doi.org/10.7554/eLife.46986