TI  - The X-ray structure of a <prot>growth hormone</prot>-<prot>prolactin</prot> receptor complex.
PG  - 478-81
AB  - The human pituitary hormones, <prot>growth hormone</prot> (<prot>hGH</prot>) and <prot>prolactin</prot> (<prot>hPRL</prot>),
      regulate a large variety of physiological processes, among which are
      growth and differentiation of muscle, bone and cartilage cells, and
      lactation. These activities are initiated by hormone-receptor binding. The
       <prot>hGH</prot>  and  <prot>hPRL</prot>  receptors ( <prot>hGHR</prot>  and  <prot>hPRLR</prot> , respectively) are single-pass
      transmembrane receptors from class 1 of the haematopoietic receptor
      superfamily. This classification is based on sequence similarity in their
      extracellular domains, notably a highly conserved pentapeptide, the
      so-called 'WSXWS box', the function of which is controversial. All ligands
      in class 1 activate their respective receptors by clustering mechanisms.
      In the case of <prot>hGH</prot>, activation involves receptor homodimerization in a
      sequential process: the active ternary complex containing one ligand and
      two receptor molecules is formed by association of a receptor molecule to
      an intermediate 1:1 complex. <prot>hPRL</prot> does not bind to the <prot>hGH</prot> receptor, but
        <prot>hGH</prot>   binds to both the  <prot>hGHR</prot>  and  <prot>hPRLR</prot> , and mutagenesis studies have shown
      that the receptor-binding sites on <prot>hGH</prot> overlap. We present here the
      crystal structure of the 1:1 complex of <prot>hGH</prot> bound to the extracellular
      domain of the <prot>hPRLR</prot>. Comparisons with the <prot>hGH</prot>-<prot>hGHR</prot> complex reveal how <prot>hGH</prot>
      can bind to the two distinctly different receptor binding surfaces.
AD  - Genentech Inc., Department of Protein Engineering, South San Francisco,
