The inhibition of hemoglobin C crystallization by hemoglobin F.
We have reported that circulating CC erythrocytes containing HbO2 C crystals exhibit little or no Hb F suggesting that Hb F may inhibit the crystallization of Hb C. We report now that Hb F inhibits in vitro crystallization of HbO2 and HbCO C when compared to the effect of Hb A in a wide range of mixture proportions. For example, while HbCO C solutions form tetragonal C crystals within 25 min, no crystals form within 2 h with 30% Hb F, whereas 550 crystals/mm3 form with 30% Hb A. Furthermore, an increase in the percent of Hb A is correlated with a greater number of orthorhombic crystal formation rather than the tetragonal morphology observed with 100% Hb C. We also report that Hb A2 (containing delta chains that exhibit 10 sequence differences with beta chains) and Hb Lepore Boston-Washington (a fusion mutant of delta and beta chains that contains only six of these differences) both inhibit Hb C crystallization. By comparing the sequences of the three inhibitory hemoglobins, we conclude that position Gln-87 in the gamma chains is, at least partially, the cause of the inhibitory effect of Hb F on the crystallization of Hb C.
D000595:Amino Acid Sequence; D003460:Crystallization; D005319:Fetal Hemoglobin / Q000502:physiology*; D006441:Hemoglobin A / Q000502:physiology; D006443:Hemoglobin A2 / Q000502:physiology; D006444:Hemoglobin C; D006455:Hemoglobins, Abnormal; D006801:Humans; D007700:Kinetics; D013329:Structure-Activity Relationship
D006455:Hemoglobins, Abnormal; C039800:hemoglobin Lepore Boston-Washington; D006444:Hemoglobin C; D006441:Hemoglobin A; D006443:Hemoglobin A2; D005319:Fetal Hemoglobin