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

Badior, Katherine E.; Casey, Joseph R.

doi:10.1016/j.bbamem.2021.183678

Cited by 14 publications

(20 citation statements)

References 89 publications

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“…Cysteine scanning mutagenesis and labeling of AE1 expressed in HEK 293 cells also indicated that these residues are extracellular (366,368). Badior and Casey (453) recently reexamined the topology of this sequence in AE1 expressed in HEK cells and found that this sequence is mainly cytoplasmic, consistent with the crystal structure, but it can reorient transiently to a conformation in which it is exposed to the extracellular medium. Binding of extracellular IgG can potentially trap this rare conformation.…”

Section: Structure and Interaction With Other Proteinsmentioning

confidence: 68%

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Cell physiology and molecular mechanism of anion transport by erythrocyte band 3/AE1

Jennings

2021

American Journal of Physiology-Cell Physiology

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The major transmembrane protein of the red blood cell, known as band 3, AE1, and SLC4A1, has two main functions: 1) catalysis of Cl-/HCO3- exchange, one of the steps in CO2 excretion; 2) anchoring the membrane skeleton. This review summarizes the 150 year history of research on red cell anion transport and band 3 as an experimental system for studying membrane protein structure and ion transport mechanisms. Important early findings were that red cell Cl- transport is a tightly coupled 1:1 exchange and band 3 is labeled by stilbenesulfonate derivatives that inhibit anion transport. Biochemical studies showed that the protein is dimeric or tetrameric (paired dimers) and that there is one stilbenedisulfonate binding site per subunit of the dimer. Transport kinetics and inhibitor characteristics supported the idea that the transporter acts by an alternating access mechanism with intrinsic asymmetry. The sequence of band 3 cDNA provided a framework for detailed study of protein topology and amino acid residues important for transport. The identification of genetic variants produced insights into the roles of band 3 in red cell abnormalities and distal renal tubular acidosis. The publication of the membrane domain crystal structure made it possible to propose concrete molecular models of transport. Future research directions include improving our understanding of the transport mechanism at the molecular level and of the integrative relationships among band 3, hemoglobin, carbonic anhydrase, and gradients (both transmembrane and subcellular) of HCO3-, Cl-, O2, CO2, pH, and NO metabolites during pulmonary and systemic capillary gas exchange.

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Section: Structure and Interaction With Other Proteinsmentioning

confidence: 68%

“…Over time, enough band 3 could become bound with IgG to mark the cell as senescent. The reorientation of residues 812–830 could therefore serve as the molecular clock for erythrocyte senescence ( 453 ). This new idea will likely be tested in future experiments and simulations.…”

Section: Ongoing Questions About Bandmentioning

confidence: 99%

Cell physiology and molecular mechanism of anion transport by erythrocyte band 3/AE1

Jennings

2021

American Journal of Physiology-Cell Physiology

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“…However, a recent study in RBCs supports and clarifies previous reports of the RBC senescent antigen, and indicate that the senescent cell antigen on Band 3 is a cryptic discontinuous epitope, requiring a conformational change for exposure to SAb. 1 We have been able to purify an IgG antibody from the RBCs of 20 normal healthy blood donors (Figure 1A) and characterize this autoantibody as primarily IgG (Figure 1B,C) with a small proportion of IgM, as indicated by Western immunoblotting (Figure 1C). This autoantibody recognizes a conformational epitope on Band 3 (Figure 1D).…”

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confidence: 96%

A naturally present autoantibody to senescent red blood cells?

2022

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“…Finally, an excellent example of the conformational dynamics of Band 3 is the senescence antigen (Badior and Casey, 2021). Early work showed that the Band 3 sequence encompassing residues 812-830 plays a role in binding endogenous senescence antibodies to aged red blood cells.…”

Section: Senescence: An Example Of Conformational Dynamics In Bandmentioning

confidence: 99%

Organization and Dynamics of the Red Blood Cell Band 3 Anion Exchanger SLC4A1: Insights From Molecular Dynamics Simulations

Kalli

Reithmeier

2022

Front. Physiol.

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Molecular dynamics (MD) simulations have provided new insights into the organization and dynamics of the red blood cell Band 3 anion exchanger (AE1, SLC4A1). Band 3, like many solute carriers, works by an alternating access mode of transport where the protein rapidly (104/s) changes its conformation between outward and inward-facing states via a transient occluded anion-bound intermediate. While structural studies of membrane proteins usually reveal valuable structural information, these studies provide a static view often in the presence of detergents. Membrane transporters are embedded in a lipid bilayer and associated lipids play a role in their folding and function. In this review, we highlight MD simulations of Band 3 in realistic lipid bilayers that revealed specific lipid and protein interactions and were used to re-create a model of the Wright (Wr) blood group antigen complex of Band 3 and Glycophorin A. Current MD studies of Band 3 and related transporters are focused on describing the trajectory of substrate binding and translocation in real time. A structure of the intact Band 3 protein has yet to be achieved experimentally, but cryo-electron microscopy in combination with MD simulations holds promise to capture the conformational changes associated with anion transport in exquisite molecular detail.

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

Cited by 14 publications

References 89 publications

Cell physiology and molecular mechanism of anion transport by erythrocyte band 3/AE1

Cell physiology and molecular mechanism of anion transport by erythrocyte band 3/AE1

A naturally present autoantibody to senescent red blood cells?

Organization and Dynamics of the Red Blood Cell Band 3 Anion Exchanger SLC4A1: Insights From Molecular Dynamics Simulations

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