血红蛋白F和血红蛋白A2对血红蛋白S聚合抑制作用的结构基础
Structural bases of the inhibitory effects of hemoglobin F and hemoglobin A2 on the polymerization of hemoglobin S.
作者信息
Nagel R L, Bookchin R M, Johnson J, Labie D, Wajcman H, Isaac-Sodeye W A, Honig G R, Schilirò G, Crookston J H, Matsutomo K
出版信息
Proc Natl Acad Sci U S A. 1979 Feb;76(2):670-2. doi: 10.1073/pnas.76.2.670.
Abstract
We have previously found that the inhibitory effect of hemoglobin F (Hb F) on the polymerization of Hb S proceeds via the formation of asymmetrical hybrid tetramers of the type alpha2betasgamma. Examination of the gelling properties of binary mixtures of Hb S and several Hb variants now shows that, among the gamma chain amino acid residues that differ from those of the beta chain, residues gamma80 (EF4) and gamma87 (F3) are at least partly responsible for this inhibition. Furthermore, we find that mixing Hb A2(alpha2delta2) with Hb S strongly inhibits gelling to an extent similar to that seen with Hb S/Hb F mixtures; this inhibition is attributable to amino acid differences between the delta and beta chain sequences at positions delta22 (B4) and delta87 (F3). Therefore, residues 22, 80, and 87 of the beta chain appear to be involved in intermolecular contact sites that stabilize the deoxy Hb S polymers.
摘要
我们之前发现，血红蛋白F（Hb F）对Hb S聚合的抑制作用是通过形成α2βsγ类型的不对称杂合四聚体来实现的。对Hb S与几种Hb变体二元混合物的胶凝特性研究表明，在与β链不同的γ链氨基酸残基中，残基γ80（EF4）和γ87（F3）至少部分地导致了这种抑制作用。此外，我们发现将Hb A2（α2δ2）与Hb S混合会强烈抑制胶凝，其程度与Hb S/Hb F混合物相似；这种抑制作用归因于δ链和β链序列在δ22（B4）和δ87（F3）位置的氨基酸差异。因此，β链的22、80和87位残基似乎参与了稳定脱氧Hb S聚合物的分子间接触位点。
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