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

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  • Author(s): Badior KE;Badior KE; Casey JR; Casey JR
  • Source:
    Biochimica et biophysica acta. Biomembranes [Biochim Biophys Acta Biomembr] 2021 Oct 01; Vol. 1863 (10), pp. 183678. Date of Electronic Publication: 2021 Jun 24.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101731713 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-2642 (Electronic) Linking ISSN: 00052736 NLM ISO Abbreviation: Biochim Biophys Acta Biomembr Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam : Elsevier
    • Subject Terms:
      Erythrocyte Aging* ; Signal Transduction*; Anion Exchange Protein 1, Erythrocyte/*chemistry; HEK293 Cells ; Humans ; Protein Conformation
    • Abstract:
      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.)
    • Grant Information:
      Canada CIHR
    • Contributed Indexing:
      Keywords: Band 3; Conformational change; Erythrocyte; Senescence
    • Accession Number:
      0 (Anion Exchange Protein 1, Erythrocyte)
    • Publication Date:
      Date Created: 20210627 Date Completed: 20211123 Latest Revision: 20211123
    • Publication Date:
      20250114
    • Accession Number:
      10.1016/j.bbamem.2021.183678
    • Accession Number:
      34175296