Basis of unique red cell membrane properties in hereditary ovalocytosis.
Hereditary ovalocytes from a Mauritian subject are extremely rigid, with a shear elastic modulus about three times that of normal cells, and have increased resistance to invasion by the malaria parasite Plasmodium falciparum in vitro. The genetic anomaly resides in band 3; the protein gives rise to chymotryptic fragments with reduced mobility in SDS/polyacrylamide gel electrophoresis, but this is a result of anomalous binding of SDS and not a higher molecular weight. Analysis of the band 3 gene reveals (1) a point mutation (Lys56----Glu), which also occurs in a common asymptomatic band 3 (Memphis) variant and governs the electrophoretic properties, and (2) a deletion of nine amino acid residues, including a proline residue, encompassing the interface between the membrane-associated and the N-terminal cytoplasmic domains. The interaction of the mutant band 3 with ankyrin appears unperturbed. The fraction of band 3 capable of undergoing translation diffusion in the membrane is greatly reduced in the ovalocytes. Cells containing the asymptomatic band 3 variant were normal with respect to all the properties that we have studied. Possible mechanisms by which a structural change in band 3 at the membrane interface could regulate rigidity are examined.
Schofield
A E
AE
Department of Biochemistry, University of Bristol, U.K.
Tanner
M J
MJ
Pinder
J C
JC
Clough
B
B
Bayley
P M
PM
Nash
G B
GB
Dluzewski
A R
AR
Reardon
D M
DM
Cox
T M
TM
Wilson
R J
RJ
D000328:Adult; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000737:chemistry / Q000502:physiology*; D001483:Base Sequence; D004548:Elasticity; D004612:Elliptocytosis, Hereditary / Q000503:physiopathology*; D004907:Erythrocyte Deformability; D004910:Erythrocyte Membrane / Q000502:physiology*; D004913:Erythrocytes, Abnormal / Q000469:parasitology; D006801:Humans; D008297:Male; D008560:Membrane Fluidity; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000254:growth & development
D001457:Anion Exchange Protein 1, Erythrocyte