Large conformational dynamics in Band 3 protein: Significance for erythrocyte senescence signalling.

Autor: Badior KE; Department of Biochemistry, Membrane Protein Disease Research Group, University of Alberta, Edmonton, Alberta T6G 2H7, Canada., Casey JR; Department of Biochemistry, Membrane Protein Disease Research Group, University of Alberta, Edmonton, Alberta T6G 2H7, Canada. Electronic address: casey@ualberta.ca.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Biomembranes [Biochim Biophys Acta Biomembr] 2021 Oct 01; Vol. 1863 (10), pp. 183678. Date of Electronic Publication: 2021 Jun 24.
DOI: 10.1016/j.bbamem.2021.183678
Abstrakt: Band 3 (Anion Exchanger 1, AE1), the predominant protein of erythrocyte membranes, facilitates Cl - /HCO 3 - exchange and anchors the plasma membrane to the cytoskeleton. The Band 3 crystal structure revealed the amino acid 812-830 region as intracellular, conflicting with protein chemical data that suggested extracellular disposition. Further, circulating senescent cell auto-antibody that cannot enter erythrocytes, binds two regions of Band 3: residues 538-554 and 812-830. To reconcile this discrepancy, we assessed localization of residues 812-830 with Band 3 expressed in HEK293 cells and human erythrocytes, using chemical labeling probes and an antibody against residues 812-830. Antibody and chemical probes revealed reorientation of 812-830 region between extracellular and intracellular. This dramatic conformational change is an intrinsic property of the Band 3 molecule, occurring when expressed in HEK293 cells and without the damage that occurs during erythrocyte circulation. Conditions used to crystallize Band 3 for structural determination did not alter conformational dynamics. Collectively, these data reveal large Band 3 conformational dynamics localized to a region previously identified as an erythrocyte senescence epitope. Surface exposure of the senescence epitope (812-830), limited by conformational dynamics, may act as the "molecular clock" in erythrocyte senescence.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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