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Symposium on the haemoglobinopathies structure of sickle-cell haemoglobin
79 (The previous number of these Transactions, 1Iol. 68, No. 1, was published on 27th Febuary, 1974) ROYAL SOCIETYOF TROPICALMEDICINE AND HYGIENE ORDINARY MEETING Manson House, Thursday, 13 December, 1973. The President, PROFESSORA. W. WOODRUFF,M.D., PH.D., F.R.C.P., D.T.M. & H., in the Chair.
SYMPOSIUM ON THE HAEMOGLOBINOPATHIES STRUCTURE OF SICKLE-CELL HAEMOGLOBIN J. T. F I N C H ANO M. F. PERUTZ M. R. C. Laboratory of Molecular Biology, Cambridge University Sickling arises as a result of a mutation which replaces glutamate 6~ by valine. The replaced residue lies at the surface of the haemoglobin molecule so that it cannot affect its internal structure. This is borne out by the isomorphism of crystals of oxyhaemoglobins A and S, and by the identity of their N M R spectra. On deoxygenation haemoglobin S becomes insoluble in the red cell and crystallizes out in the form of long, straight fibres. These may extend through most of the length of the siclded cell, forming either square or hexagonally packed bundles with lattice constants of 170-180 A. Each fibre is a tube made up of 6 thin filaments which are wound around the tubular surface with a helical pitch of about 3000 A. Each filament is a string of single haemoglobin molecules linked end to end at intervals of 62 A in dry and 64 A in wet fibres. Molecules in neighbouring filaments are in longitudinal register so that they form fiat hexagonal rings; these rings are stacked so that successive ones are rotated about the fibre axis by 7.3 °. The whole structure repeats after about 8 rings. In this structure each molecule makes contact with 4 neighbours. The orientation of the molecules can be deduced from comparisons of the polarization dichroism of siclded cells and of crystals of deoxyhaemoglobin A, but the precise points of contact between neighbouring moleoales are still unclear. Filaments similar to those found in siclded cells are also observed in normal deoxygenated erythrocytes, but in much lower concentration and aggregated into fibres of irregular diameter. No filaments appear in oxygenated sickle or normal, adult cells, nor in oxygenated or deoxygenated foetal cells. REFERENCE FINCH, J. T., PERUTZ, M. F., BERTLES,J. F. & DOBLER,J. (1973) Proc. nat. Acad. Sd. USA, 70, 718.
SYMPOSIUM ON THE HAEMOGLOBINOPATHIES STRUCTURE OF SICKLE-CELL HAEMOGLOBIN J. T. F I N C H ANO M. F. PERUTZ M. R. C. Laboratory of Molecular Biology, Cambridge University Sickling arises as a result of a mutation which replaces glutamate 6~ by valine. The replaced residue lies at the surface of the haemoglobin molecule so that it cannot affect its internal structure. This is borne out by the isomorphism of crystals of oxyhaemoglobins A and S, and by the identity of their N M R spectra. On deoxygenation haemoglobin S becomes insoluble in the red cell and crystallizes out in the form of long, straight fibres. These may extend through most of the length of the siclded cell, forming either square or hexagonally packed bundles with lattice constants of 170-180 A. Each fibre is a tube made up of 6 thin filaments which are wound around the tubular surface with a helical pitch of about 3000 A. Each filament is a string of single haemoglobin molecules linked end to end at intervals of 62 A in dry and 64 A in wet fibres. Molecules in neighbouring filaments are in longitudinal register so that they form fiat hexagonal rings; these rings are stacked so that successive ones are rotated about the fibre axis by 7.3 °. The whole structure repeats after about 8 rings. In this structure each molecule makes contact with 4 neighbours. The orientation of the molecules can be deduced from comparisons of the polarization dichroism of siclded cells and of crystals of deoxyhaemoglobin A, but the precise points of contact between neighbouring moleoales are still unclear. Filaments similar to those found in siclded cells are also observed in normal deoxygenated erythrocytes, but in much lower concentration and aggregated into fibres of irregular diameter. No filaments appear in oxygenated sickle or normal, adult cells, nor in oxygenated or deoxygenated foetal cells. REFERENCE FINCH, J. T., PERUTZ, M. F., BERTLES,J. F. & DOBLER,J. (1973) Proc. nat. Acad. Sd. USA, 70, 718.