Molecular Defect of the Band 3 Protein in Southeast Asian Ovalocytosis

Abstract

The red cells in Southeast Asian ovalocytosis carry a structurally and functionally abnormal band 3 protein. This molecular defect may underlie the increased rigidity of the red cells and their resistance to invasion by malaria parasites.

Molecular basis for membrane rigidity of hereditary ovalocytosis. A novel mechanism involving the cytoplasmic domain of band 3.

“…Following the seminal observation ofLiu et al (13) that the molecular defect in ovalocytes resides in band 3, and our own observation that marked changes in membrane material behavior can be induced by alterations in the cytoplasmic domain of an integral membrane protein (26,27), we focused our attention on the cytoplasmic domain ofband 3. PCR analysis on the first 1448 nucleotides ofband 3 cDNA including the 5' untranslated region and extending to the beginning of the second transmembrane domain, showed a deletion of 27 nucleotides (nt 1198 to nt 1224) in reticulocyte cDNA from blood of Malayan individuals with hereditary ovalocytosis.…”

“…However, detailed biochemical analysis failed to identify a defect in any ofthese skeletal proteins. The underlying molecular defect in ovalocytes remained a mystery until Liu et al (13) made the surprising observation that the ovalocytic phenotype was linked to a structural polymorphism in band 3 protein, the red cell anion transporter. However, the mechanism by which a mutation in band 3 can induce increased membrane rigidity has yet to be defined.…”

Expression, purification, and characterization of the functional dimeric cytoplasmic domain of human erythrocyte band 3 in Escherichia coli

“…Cdb3 participates in the control of membrane mechanical stability via its pH-dependent association with ankyrin (Thevenin & Low, 1990;Low et al, 1991). Perturbations of this interaction, whether by artificial means or through natural mutation, can dramatically affect the rigidity and stability of the cell (Liu et al, 1990;Low et al, 1991). Cdb3 also binds and regulates the activities of several glycolytic enzymes by associating reversibly with the enzymes in an inhibitory complex (Low et al, 1987).…”

Coinheritance of Southeast Asian ovalocytosis and the β-thalassemia trait in a Malay family

“…They mediate anion transport across the membrane and respiration of carbon dioxide, and they provide a principle biding sites for ankyrin, a protein that anchors the cytoskeletal spectrin to the red cell membrane. The truncated variant of band-3 transmembrane protein (B3Δ27) removes nine amino acids from residues 400-408 at the boundary between the cytoplasmic domain and the first transmembrane domain in RBCs [6,7]. As a result, the band-3 glycoproteins in SAO remain tightly bound to ankyrin, reducing the lateral mobility of the membrane and affecting other membrane bound functions.…”

“…It is an asymptomatic hereditary autosomal dominant disorder characterized by macro-ovalocytes and stomatocytes constituting 25% of the cells in peripheral blood smears (PBS). The underlying molecular abnormality is due to deletion of nine amino acids from the transmembrane protein called band-3, which has various structural and functional consequences [6,7]. β-Thalassemia is a RBC disorder caused by a mutant allele in the β-globin gene (HBB) that leads to impaired synthesis of β-globin peptides [8].…”