Abstract
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.
Original language | English |
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Pages (from-to) | 949-958 |
Number of pages | 10 |
Journal | Journal of Molecular Biology |
Volume | 223 |
Issue number | 4 |
DOIs | |
Publication status | Published - 20 Feb 1992 |
Bibliographical note
Funding Information:We thank Dr Elias Zintzaras for statistical evaluation of the diffusion data, Kate Kirwan for all the artwork and photography and Dr D. Yannoukakos for communicating unpublished data. This work was supported by the UNDP/World Bank /World Health Organization Special Programme for Research and Training in Tropical Diseases (G.N., A.D. and W.G.) and by the Medical Research Council (M.T.). A.E.S. held a Wellcome Prize Studentship and B.C. an MRC Training Scholarship and received support from the Jules Thorne Charitable Trust.
Keywords
- band 3
- erythrocyte membrane
- ovalocytosis
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Molecular Biology