COMPARISON OF THE INTERMEDIATE COMPLEXES OF HUMAN GROWTH-HORMONE BOUND TO THE HUMAN GROWTH-HORMONE AND PROLACTIN RECEPTORS

The crystal structures of complexes of human growth hormone (hGH) with the growth hormone and prolactin receptors (hGHR and hPRLR, respectiv ely), together with the mutational data available for these systems, s uggest that an extraordinary combination of conformational adaptabilit y, together with finely tuned specificity, governs the molecular recog nition processes operative in these systems. On the one hand, in the a ctive 1:2 ligand-receptor complexes, 2 copies of the same receptor use the identical set of binding determinants to recognize topographicall y different surfaces on the hormone. On the other hand, comparing the 1:1 hGH-hGHR and hGH-hPRLR complexes, 2 distinct receptors use this sa me set of binding determinants to interact with the identical binding site on the ligand, even though few residues among the binding determi nants are conserved. The structural evidence demonstrates that this ve rsatility is accomplished by local conformational flexibility of the b inding loops, allowing adaptation to different binding environments, t ogether with rigid-body movements of the receptor domains, necessary f or the creation of specific interactions with the same binding site.