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CryoEM structures of anion exchanger 1 capture multiple states of inward- and outward-facing conformations

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 tran...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9751308/
https://www.ncbi.nlm.nih.gov/pubmed/36517642
http://dx.doi.org/10.1038/s42003-022-04306-8
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author 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
author_facet 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
author_sort Zhekova, Hristina R.
collection PubMed
description 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.
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spelling pubmed-97513082022-12-16 CryoEM structures of anion exchanger 1 capture multiple states of inward- and outward-facing conformations 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 Commun Biol Article 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. Nature Publishing Group UK 2022-12-14 /pmc/articles/PMC9751308/ /pubmed/36517642 http://dx.doi.org/10.1038/s42003-022-04306-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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
CryoEM structures of anion exchanger 1 capture multiple states of inward- and outward-facing conformations
title CryoEM structures of anion exchanger 1 capture multiple states of inward- and outward-facing conformations
title_full CryoEM structures of anion exchanger 1 capture multiple states of inward- and outward-facing conformations
title_fullStr CryoEM structures of anion exchanger 1 capture multiple states of inward- and outward-facing conformations
title_full_unstemmed CryoEM structures of anion exchanger 1 capture multiple states of inward- and outward-facing conformations
title_short CryoEM structures of anion exchanger 1 capture multiple states of inward- and outward-facing conformations
title_sort cryoem structures of anion exchanger 1 capture multiple states of inward- and outward-facing conformations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9751308/
https://www.ncbi.nlm.nih.gov/pubmed/36517642
http://dx.doi.org/10.1038/s42003-022-04306-8
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