Human growth hormone-binding protein

Fig. 7. Three different binding sites used by the immunoglobulin-like proteins tbe PapD chaperone, the antigen-binding fragment of an immunoglobulin (Fab ), and the human growth hormone-binding protein (hCHbp). Each immunoglobulin-like domain is...

Fig. 4 CH/jt interactions observed in human growth hormone-binding protein (PDB code 3HHR) Lys2l5/Tyr222/Arg213/Phe225/ Arg211/Trpl86/Lysl79 (From Ref [68J, Fig 10.)...

An example is given in Fig. 4 for a sequence of CH/ti bonds observed in human growth hormone-binding protein. Notice that the methylene hydrogens in Lys and Arg arc involved in a stacked manner with aromatic residues, Phe, Tyr, and Trp. 

Gro 1C-/actor signaling. Human growth hormone binds to a cell-surface membrane protein that is not a receptor tyrosine kinase. The intracellular domain of the receptor can bind other proteins inside the cell. Furthermore, studies indicate that the receptor is monomeric in the absence of hormone but dimerizes on hormone binding. Propose a possible mechanism for growth-hormone signaling. 

Baumann G, Amburn K D, Buchanan T A (1987). The effect of circulating growth hormone-binding protein on metabolic clearance, distribution, and degradation of human growth hormone. /. Clin. Endocrinol. Metab. 64 657-660. 

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... 

Lastly, it has been shown that in rare cases trisulfide bridges (Cys-SSS-Cys) can be found as hydrophobic variants of recombinant proteins. The experimental mass of such a trisulfide-bridged peptide would be increased by 32 amu. Andersson et al.125 have described this phenomenon for recombinant human growth hormone during expression in E. coli. However, the receptor binding properties were not affected by this trisulfide modification. 

Human growth hormone (hGH) is a polypeptide with 191 amino acids. It is secreted by the pituitary gland. This hormone stimulates the production of insulin-like growth factor-1 (IGF-1) from the liver. Most of the positive effects of hGH are mediated by the IGF-1 system, which also includes specific binding proteins. 

Verkhivker GM, Bouzida D, Gehlhaar DK, Rejto PA, Freer ST, Rose PM(2003) Computational detection of the binding-site hot spot at the remodelled human growth hormone-receptor interface, Proteins, 53 201-219... 

Human growth hormone (GHl, Fig. 1), epidermal growth factor (EGF), insnlin (INS), platelet-derived growth factor (PDGF), and many cytokines bind receptors that activate intracellular tyrosine kinase activity. The major isoform of GHl is a protein of 191 amino acids (22 KDa) that fnnctions in part to stimulate the growth of bone and internal organs in children. As shown in Fig. 1, the human growth hormone receptor (GHR), which is a member of the cytokine-hematopoietin receptor superfamily. 

The classical parameters of >90% talc adsorption and TCA precipitation, with 3% agreement between the talc and TCA values, and <25% binding to resin are appropriate for polypeptide hormones with a certain chemical composition, including most anterior pituitary hormones. We have found, so far, two exceptions to the above parameters the S variant form of human growth hormone (hGH-S) and human FSH (all preparations). These are acidic proteins and show a decreased adsorption to talc and an increased binding to resin. 

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