Hormone dimerization

Dimerization is a process necessary for the receptor to carry out its interaction with DNA and to initiate the response to the hormone. Dimerization occurs when the receptor monomer has freed itself of hsp90 and the other accompanying proteins forming the structure of the native receptor. Moreover, binding to the hormone provides the receptor with the necessary three-dimensional structure to produce the interaction between the two receptor monomers (Kuiper et al. 1996 O Malley 1990). 

Poly(ADP-ribose) polymerase may also have a role in regulating the activity of nuclear-acting hormone receptors it hinds directly to retinoid X receptors (Section 2.3.2.1) andinhihits the transcriptional activity of retinoid X receptor-thyroid hormone dimers, it also acts as a transcription factor in pancreatic /S-islet cells (Miyamoto et al., 1999). 

One glycosylation site exists on the P suburhts of human LH [53664-53-2 and TSH [64365-92-OJ ie, Asn-30 (Fig. 4). In some species, Asn-13 of LH-P is glycosylated (48). FSH-P suburnt [58857-12-8] is glycosylated at two sites, Asn-13 and 30. Based on interactions of synthetic peptides with the LH receptor, loops formed by P93—100 and P38—57 may be essential for hormone bioactivity (48). Highly conserved sequences between residues 31—37 have been implicated in the formation of the a—P suburnt dimer (48), which is absolutely necessary for the expression of bioactivity. 

The human growth hormone induces dimerization of its cognate receptor... 

Dimerization of the growth hormone receptor is a sequential process... 

EMPl, selected by phage display from random peptide libraries, demonstrates that a dimer of a 20-residue peptide can mimic the function of a monomeric 166-residue protein. In contrast to the minimized Z domain, this selected peptide shares neither the sequence nor the structure of the natural hormone. Thus, there can be a number of ways to solve a molecular recognition problem, and combinatorial methods such as phage display allow us to sort through a multitude of structural scaffolds to discover novel solutions. 

Cunninghum BC, Ultsch M, De Vos AM, Mulkerrin MG, Clauser KR, Wells JA. Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule. Science 1991 254 821-825. 

The crystal structures of monomeric ligands such as GH and EPO in complex with their respective receptors show that these hormones are bivalent and one ligand binds simultaneously to two receptor molecules to form a 1 2 (ligand receptor) complex. Receptor dimerization is further stabilized by additional receptor-receptor interactions. 

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