Kossiakoff A A, Somers W, Ultsch M, Andow K, Muller Y A, De Vos A M
Department of Protein Engineering, Genentech, Inc., South San Francisco, California 94080.
Protein Sci. 1994 Oct;3(10):1697-705. doi: 10.1002/pro.5560031008.
The crystal structures of complexes of human growth hormone (hGH) with the growth hormone and prolactin receptors (hGHR and hPRLR, respectively), together with the mutational data available for these systems, suggest that an extraordinary combination of conformational adaptability, together with finely tuned specificity, governs the molecular recognition processes operative in these systems. On the one hand, in the active 1:2 ligand-receptor complexes, 2 copies of the same receptor use the identical set of binding determinants to recognize topographically different surfaces on the hormone. On the other hand, comparing the 1:1 hGH-hGHR and hGH-hPRLR complexes, 2 distinct receptors use this same set of binding determinants to interact with the identical binding site on the ligand, even though few residues among the binding determinants are conserved. The structural evidence demonstrates that this versatility is accomplished by local conformational flexibility of the binding loops, allowing adaptation to different binding environments, together with rigid-body movements of the receptor domains, necessary for the creation of specific interactions with the same binding site.
人生长激素（hGH）与生长激素受体和催乳素受体（分别为hGHR和hPRLR）复合物的晶体结构，以及这些系统可用的突变数据表明，构象适应性与精细调节的特异性的非凡组合，支配着这些系统中起作用的分子识别过程。一方面，在活性1:2配体-受体复合物中，同一受体的2个拷贝使用相同的一组结合决定簇来识别激素上拓扑结构不同的表面。另一方面，比较1:1的hGH-hGHR和hGH-hPRLR复合物，2种不同的受体使用这同一组结合决定簇与配体上相同的结合位点相互作用，尽管结合决定簇中几乎没有残基是保守的。结构证据表明，这种多功能性是通过结合环的局部构象灵活性来实现的，这允许适应不同的结合环境，同时受体结构域进行刚体运动，这对于与相同结合位点形成特异性相互作用是必要的。
