期刊
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
卷 1863, 期 10, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbamem.2021.183678
关键词
Band 3; Senescence; Erythrocyte; Conformational change
资金
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council-supported International Research Training Group in Membrane Biology
Band 3, the predominant protein in erythrocyte membranes, undergoes significant conformational dynamics between intracellular and extracellular regions, potentially playing a crucial role in erythrocyte aging.
Band 3 (Anion Exchanger 1, AE1), the predominant protein of erythrocyte membranes, facilitates Cl-/HCO3- 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.
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