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 (beta6 Glu-->Val) fiber is formed by the packing of double st rands which constitute the basic unit of the deoxyHb S polymer. The sp ecific interaction responsible for the stabilization of the double str and involves the mutated beta6 Val side chain (lateral contact). Recom binant Hb beta6 Glu-->Ala and the double mutant beta6 Glu-->Ala, 23 Va l-->Ile exhibit a decreased solubility compared to Hb A. While the Hb beta6 Ala does not polymerize, the association of the beta23 Val-->Ile mutation at the axial contact allows the double mutant to polymerize. These results show that : (1) the hydrophobic interactions between do nor and acceptor sites depend on both the hydrophobicity and the stere ospecificity of the amino acid side chain at the beta6 position ; (2) increasing the hydrophobic interactions at the axial contact (connecti ng molecules along the same strand) result in an increased stability o f the lateral contact between filaments.