A test of the role of the proximal histidines in the Perutz model for cooperativity in haemoglobin

被引:72
作者
Barrick, D
Ho, NT
Simplaceanu, V
Dahlquist, FW
Ho, C
机构
[1] UNIV OREGON, INST MOL BIOL, EUGENE, OR 97403 USA
[2] CARNEGIE MELLON UNIV, DEPT BIOL SCI, PITTSBURGH, PA 15213 USA
关键词
D O I
10.1038/nsb0197-78
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human haemoglobin has long been a paradigm for cooperative ligand binding and allostery. Through analysis of the crystal structures of deoxyhaemoglobin and liganded haemoglobin, Perutz proposed a model for cooperativity in which the bond between the proximal histidine and the protein couples haem rearrangements to protein structure rearrangements. Here we test this model by deleting the bonds between the histidine imidazole ride chain and the polypeptide, This detachment method allows us to determine directly the contribution of proximal histidine coupling to cooperativity of distal ligand binding, Proximal detachment significantly increases ligand affinity reduces cooperativity, and prevents quaternary structure switching, in accord with the Perutz model. Residual cooperativity indicates that additional haem communication pathways exist that do not involve the proximal histidine coupling mechanism.
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页码:78 / 83
页数:6
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