Effects of the alpha 20 mutation on the polymerization of Hb S.
The contribution of the alpha 20 residues in intermolecular contacts present in hemoglobin S fibers was investigated with mixtures of Hb Le Lamentin alpha 2(20)His----Gln beta 2A and of hemoglobin S alpha 2A beta 2(6)Glu----Val and with artificial hybrids alpha 2(20)His----Gln beta 2(6)Glu----Val. This study showed an increased solubility and delay time of polymerization of Hb S in solution only when the mutation at the alpha 20 residue is cis to the beta 6 Val contact. No modification of the polymerization process occurs when the mutation is trans to this beta 6 Val contact. This result is in agreement with the crystal model of Wishner and Love, who showed that one of the two alpha 20 residues of the Hb S tetramer was involved in an axial contact between hemoglobin S molecules in the crystals of Hb S ( Wishner , B.C., Ward, K.B., Lattman , E.E. and Love, W.E. (1975) J. Mol. Biol. 98, 179-194). The present observation is a new illustration of the validity of the crystal model for the structure of the fibers based on pairs of double filaments.
D005914:Globins / Q000235:genetics*; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D009154:Mutation; D010108:Oxyhemoglobins; D011108:Polymers; D011487:Protein Conformation; D012995:Solubility; D013329:Structure-Activity Relationship
D006451:Hemoglobin, Sickle; D010108:Oxyhemoglobins; D011108:Polymers; D005914:Globins