Growth hormone complex

Schiffer, C., Ultsch, M., Walsh, S., Somers, W., De Vos, A. M., and Kossiakoff, A. (2002). Structme of a phage display-derived variant of human growth hormone complexed to two copies of the extracellular domain of its receptor Evidence for strong structural coupling between receptor binding sites./. Mol. Biol. 316(2), 277-289. 

In contrast, a noteworthy difference between prolactin and growth hormone complexes is that the oPL-rPRLR EGD2 interface contains nine... 

Human growth hormone is a very complex molecule biologically. Several diverse biological activities such as anaboHc, insulin-like, diabetogenic, and lactogenic activities have been ascribed to hGH, which also appears to promote water and salt retention. An in-depth discussion of these activities may be found in several excellent reviews available in the Hterature (34—36). 

Figure 13.20 Ribbon diagram of the structure of a 1 2 complex between the human growth hormone and the extracellular domains of two receptor molecules. The two receptor molecules (blue) bind the hormone (red) with essentially the same loop regions (yellow).

The prolactin receptor, PER, which regulates milk production in mammals, belongs to the same receptor class as the growth hormone receptor. In addition to binding the hormone prolactin, PER also binds and is activated by growth hormone. The extracellular domain of PER forms a very stable 1 1 complex with growth hormone in solution this complex has been crystallized and its structure determined (Figure 13.21). We shall compare this structure with the 1 2 complex of the same hormone with GHR. 

Figure 13.22 Hormone-receptor interactions involving the domain-domain linker region in the receptor, (a) Interactions between the growth hormone (red) and the growth hormone receptor (blue) linker region. Glu 127 of the receptor forms a salt bridge to Arg 167 in the hormone, (b) The same interaction area in the growth hormone (red)-prolactin receptor (green) complex. The displacement of the linker region due to differences in the domain orientations have brought Asp 124 in the prolactin receptor into contact with Arg 167 of the hormone. (Adapted from W. Somers et al.. Nature 372 478-481, 1994.)...

De Vos, A.M., Ultsch, M., Kossiakoff, A.A. Human growth hormone and extracellular domain of its receptor crystal structure of the complex. Science 255 306-312,... 

Cytokine receptors that couple to the JAK-STAT Pathway decode the signaling though hematopoietic cytokines (erythropoietin, thrombopoietin, colony-stimulating factors), prolactin, growth hormone, the a-, (3- and y- interferons, and a number of immunomodulatory interleukins [3], They form homodimetic or heterodimeric receptor complexes, which after ligandbinding recruit and activate isotypes of Janus kinases (JAKs). Activated JAKs in turn... 

The recruitment of zinc for a structural role, or to activate an enzyme, has been observed. The zinc ion induces the dimerization of human growth hormone (hGH), with two Zn ions associated per dimer of hGH. This is confirmed by replacement of possible zinc binding residues resulting in weakened binding of the zinc ion. Formation of a zinc-hGH dimeric complex may be important for storage of hGH in secretory granules.975 In a toxic role, anthrax lethal factor is one of the three components of the secreted toxin and is a zinc-dependent protease that cleaves a protein kinase and causes lysis of macrophages.976... 

Add an aliquot of the DSS or BS3 solution to the reaction medium to obtain a final concentration of 0.5-5mM. Note Simons et al. (1999) successfully used a concentration of 0.5 mM BS3 with Madin-Darby canine kidney (MDCK) cells permanently expressing a GPI-anchored form of growth hormone decay accelerating factor (GH-DAF) to crosslink the protein interaction complexes on the cell surfaces. 

An example of the complexity involved in the regulation of nuclear hormone receptors is shown in the case of the ER in the liver. Its synthesis is induced by estradiol, growth hormone, thyroid hormones, and glucocorticoids. 

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