Polymerisation of haemoglobin SA hybrid tetramers

Abstract

ERYTHROCYTE sickling and gelation of concentrated solutions of deoxyhaemoglobin (Hb) S (α₂β₂^{6 Val}) results from helical polymerisation of the tetramers, with a spatial orientation approximated by recent ultrastructural and optical studies. Earlier observations of the gelling behaviour of Hb S or Hb C Harlem (α₂β₂^{6Va1, 73Asn}) mixed with Hb A or other haemoglobins gave indirect evidence concerning intertetrameric contact sites, and we proposed that only one β6 valine-determined site was active per tetramer, the other β chain providing different polymer contacts^1,2. Our arguments required that asymmetrical hybrids (for example α₂β^Aβ^S) occurred in Hb mixtures; their long-suspected presence has recently been established^3–5, but the dissociation equilibria by which these hybrids form (Fig. 1) hinders their isolation and direct testing of their ability to polymerise. To circumvent this difficulty we have prepared Hb SA hybrids cross-linked intratetramerically to prevent dissociation, and have found them capable of polymer and gel formation quite similar to that of Hb S.