Bicarbonate transporter protein
|HCO3- transporter family|
a low energy structure for the final cytoplasmic loop of band 3, nmr, minimized average structure
|Band 3 cytoplasmic domain|
crystal structure of the cytoplasmic domain of human erythrocyte band-3 protein
In molecular biology, bicarbonate transporter proteins are proteins which transport bicarbonate. Bicarbonate (HCO3 −) transport mechanisms are the principal regulators of pH in animal cells. Such transport also plays a vital role in acid-base movements in the stomach, pancreas, intestine, kidney, reproductive organs and the central nervous system. Functional studies have suggested four different HCO3 − transport modes. Anion exchanger proteins exchange HCO3 − for Cl− in a reversible, electroneutral manner. Na+/HCO3 − co-transport proteins mediate the coupled movement of Na+ and HCO3 − across plasma membranes, often in an electrogenic manner. Na+ driven Cl−/HCO3 − exchange and K+/HCO3 − exchange activities have also been detected in certain cell types, although the molecular identities of the proteins responsible remain to be determined.
Sequence analysis of the two families of HCO3 − transporters that have been cloned to date (the anion exchangers and Na+/HCO3 − co-transporters) reveals that they are homologous. This is not entirely unexpected, given that they both transport HCO3 − and are inhibited by a class of pharmacological agents called disulphonic stilbenes. They share around ~25-30% sequence identity, which is distributed along their entire sequence length, and have similar predicted membrane topologies, suggesting they have ~10 transmembrane (TM) domains.
A conserved domain is found at the C terminus of many bicarbonate transport proteins. It is also found in some plant proteins responsible for boron transport. In these proteins it covers almost the entire length of the sequence.
The Band 3 anion exchange proteins that exchange bicarbonate are the most abundant polypeptide in the red blood cell membrane, comprising 25% of the total membrane protein. The cytoplasmic domain of band 3 functions primarily as an anchoring site for other membrane-associated proteins. Included among the protein ligands of this domain are ankyrin, protein 4.2, protein 4.1, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphofructokinase, aldolase, hemoglobin, hemichromes, and the protein tyrosine kinase (p72syk).
- Kopito RR (1990). "Molecular biology of the anion exchanger gene family". Int. Rev. Cytol. 123: 177–99. doi:10.1016/S0074-7696(08)60674-9. PMID 2289848.
- Boron WF, Fong P, Hediger MA, Boulpaep EL, Romero MF (June 1997). "The electrogenic Na/HCO3 cotransporter". Wien. Klin. Wochenschr. 109 (12-13): 445–56. PMID 9261985.
- Burnham CE, Amlal H, Wang Z, Shull GE, Soleimani M (August 1997). "Cloning and functional expression of a human kidney Na+:HCO3- cotransporter". J. Biol. Chem. 272 (31): 19111–4. doi:10.1074/jbc.272.31.19111. PMID 9235899.
- Takano J, Noguchi K, Yasumori M, Kobayashi M, Gajdos Z, Miwa K, Hayashi H, Yoneyama T, Fujiwara T (November 2002). "Arabidopsis boron transporter for xylem loading". Nature. 420 (6913): 337–40. doi:10.1038/nature01139. PMID 12447444.
- Zhang, D.; Kiyatkin, A.; Bolin, J. T.; Low, P. S. (2000). "Crystallographic structure and functional interpretation of the cytoplasmic domain of erythrocyte membrane band 3". Blood. 96 (9): 2925–2933. PMID 11049968.