Affiliation:
1. Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
Abstract
The major transmembrane protein of the red blood cell, known as band 3, AE1, and SLC4A1, has two main functions: 1) catalysis of Cl−/[Formula: see text] exchange, one of the steps in CO2 excretion, and 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 [Formula: see text], Cl−, O2, CO2, pH, and nitric oxide (NO) metabolites during pulmonary and systemic capillary gas exchange.
Funder
HHS | NIH | National Institute of General Medical Sciences
University of Iowa
University of Texas Medical Branch
University of Arkansas for Medical Sciences
Publisher
American Physiological Society
Cited by
28 articles.
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