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The N-terminal 11 amino acids of human erythrocyte band 3 are critical for aldolase binding and protein phosphorylation: implications for band 3 function
- Source :
- Blood; December 2005, Vol. 106 Issue: 13 p4359-4366, 8p
- Publication Year :
- 2005
-
Abstract
- The 911 amino acid band 3 (SLC4A1) is the major intrinsic membrane protein of red cells and is the principal CL-/HCO3-exchanger. The N-terminal cytoplasmic domain of band 3 anchors the spectrin-based membrane skeleton to the lipid bilayer through its interaction with ankyrin and also binds glycolytic enzymes and hemoglobin. We identified a son of a consanguineous marriage with severe anemia in association with marked deficiency of band 3 (12% ± 4% of normal). Direct nucleotide sequencing of SLC4A1gene demonstrated a single base substitution (T → C) at position + 2 in the donor splice site of intron 2, resulting in the generation of a novel mutant protein. Biochemical characterization of the mutant protein showed that it lacked the first 11 N-terminal amino acids (band 3 Neapolis). The expression of the mutant protein resulted in the complete absence of membrane-bound aldolase, and the mutant band 3 could not be tyrosine phosphorylated. The ability of the malarial parasite P falciparumto invade these red cells was significantly decreased. The identification of a novel band 3 mutant and its structural and functional characterization enabled us to identify pivotal roles for the 11 N-terminal amino acids in several protein functions and, in turn, in red-cell physiology.
Details
- Language :
- English
- ISSN :
- 00064971 and 15280020
- Volume :
- 106
- Issue :
- 13
- Database :
- Supplemental Index
- Journal :
- Blood
- Publication Type :
- Periodical
- Accession number :
- ejs56978185
- Full Text :
- https://doi.org/10.1182/blood-2005-07-2806