[Polymerization and solubility of recombinant hemoglobins alpha 2 beta 2 6 Glu-->Ala (Hb Makassar) and alpha 2 beta 2 6 Glu-->Ala, 23 Val-->Ile].

The Hb S (beta 6 Glu-->Val) fiber is formed by the packing of double strands which constitute the basic unit of the deoxyHb S polymer. The specific interaction responsible for the stabilization of the double strand involves the mutated beta 6 Val side chain (lateral contact). Recombinant Hb beta 6 Glu-->Ala and the double mutant beta 6 Glu-->Ala, 23 Val-->Ile exhibit a decreased solubility compared to Hb A. While the Hb beta 6 Ala does not polymerize, the association of the beta 23 Val-->Ile mutation at the axial contact allows the double mutant to polymerize. These results show that: (1) the hydrophobic interactions between donor and acceptor sites depend on both the hydrophobicity and the stereospecificity of the amino acid side chain at the beta 6 position; (2) increasing the hydrophobic interactions at the axial contact (connecting molecules along the same strand) result in an increased stability of the lateral contact between filaments.