Bhatt Veer S, Zaldívar-López Sara, Harris David R, Couto C Guillermo, Wang Peng G, Palmer Andre F
Biophysics Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
Acta Crystallogr D Biol Crystallogr. 2011 May;67(Pt 5):395-402. doi: 10.1107/S0907444911006044. Epub 2011 Apr 13.
This study presents the crystal structure of Greyhound hemoglobin (GrHb) determined to 1.9 Å resolution. GrHb was found to crystallize with an α₁β₁ dimer in the asymmetric unit and belongs to the R2 state. Oxygen-affinity measurements combined with the fact that GrHb crystallizes in the R2 state despite the high-salt conditions used for crystallization strongly indicate that GrHb can serve as a model high-oxygen-affinity hemoglobin (Hb) for higher mammals, especially humans. Structural analysis of GrHb and its comparison with the R2-state of human Hb revealed several regions that can potentially contribute to the high oxygen affinity of GrHb and serve to rationalize the additional stability of the R2-state of GrHb. A previously well studied hydrophobic cluster of bar-headed goose Hb near α119 was also incorporated in the comparison between GrHb and human Hb. Finally, a structural comparison with generic dog Hb and maned wolf Hb was conducted, revealing that in contrast to GrHb these structures belong to the R state of Hb and raising the intriguing possibility of an additional allosteric factor co-purifying with GrHb that can modulate its quaternary structure.
本研究展示了分辨率达1.9 Å的灵缇血红蛋白（GrHb）的晶体结构。发现GrHb在不对称单元中以α₁β₁二聚体形式结晶，属于R2状态。尽管结晶过程中使用了高盐条件，但GrHb仍以R2状态结晶，结合氧亲和力测量结果强烈表明，GrHb可作为高等哺乳动物尤其是人类的高氧亲和力血红蛋白（Hb）模型。对GrHb的结构分析及其与人类Hb的R2状态的比较揭示了几个可能有助于GrHb高氧亲和力的区域，并有助于解释GrHb的R2状态的额外稳定性。在GrHb与人类Hb的比较中，还纳入了先前对斑头雁Hb靠近α119处一个研究充分的疏水簇。最后，对GrHb与普通犬Hb和鬃狼Hb进行了结构比较，结果表明与GrHb不同，这些结构属于Hb的R状态，这增加了一种有趣的可能性，即有一个额外的变构因子与GrHb共纯化，可调节其四级结构。
