[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.
Pagnier
J
J
INSERM U299, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
Bihoreau
M T
MT
Baudin
V
V
Edelstein
S J
SJ
Poyart
C
C
D006454:Hemoglobins / Q000378:metabolism*; D066298:In Vitro Techniques; D011108:Polymers; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D012995:Solubility
D006454:Hemoglobins; D011108:Polymers; D011993:Recombinant Fusion Proteins