We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
CryoEM structures of anion exchanger 1 capture multiple states of inward- and outward-facing conformations.
- Authors
Zhekova, Hristina R.; Jiang, Jiansen; Wang, Weiguang; Tsirulnikov, Kirill; Kayık, Gülru; Khan, Hanif Muhammad; Azimov, Rustam; Abuladze, Natalia; Kao, Liyo; Newman, Debbie; Noskov, Sergei Yu.; Tieleman, D. Peter; Hong Zhou, Z.; Pushkin, Alexander; Kurtz, Ira
- Abstract
Anion exchanger 1 (AE1, band 3) is a major membrane protein of red blood cells and plays a key role in acid-base homeostasis, urine acidification, red blood cell shape regulation, and removal of carbon dioxide during respiration. Though structures of the transmembrane domain (TMD) of three SLC4 transporters, including AE1, have been resolved previously in their outward-facing (OF) state, no mammalian SLC4 structure has been reported in the inward-facing (IF) conformation. Here we present the cryoEM structures of full-length bovine AE1 with its TMD captured in both IF and OF conformations. Remarkably, both IF-IF homodimers and IF-OF heterodimers were detected. The IF structures feature downward movement in the core domain with significant unexpected elongation of TM11. Molecular modeling and structure guided mutagenesis confirmed the functional significance of residues involved in TM11 elongation. Our data provide direct evidence for an elevator-like mechanism of ion transport by an SLC4 family member. CryoEM structures and computational modeling of bovine anion exchanger 1 in both inward and outward facing conformations reveal an elevator-like mechanism of ion transport by a solute carrier ion transport family 4 member.
- Subjects
ERYTHROCYTES; ION transport (Biology); MOLECULAR structure; MEMBRANE proteins; CELL morphology
- Publication
Communications Biology, 2022, Vol 5, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-022-04306-8