Growth hormone receptor homodimerization

The growth hormone structure established the architecture of the site I and II interactions in a homodimeric receptor complex. The viral and human IL-6 complexes with gplSO extend this paradigm to heterodimeric complexes but also elaborate the modular epitope concept by adding the site III. It is clear from the gplSO complexes that in the case of the HHV-8 IL-6, a site II is used for the gplSO GHR contact. In the human structure, a site I is used for the a. receptor and a site II is used for the gplSO GHR interaction. Similar to GH, in the human IL-6 structure, precomplexation... 

The role of receptor homodimerization is more complicated than simply bringing the cytoplasmic elements of the receptors together. For example, structural studies of EPO and EPO-R indicate that a function of the hormone is to establish a fairly exact receptor alignment, as well as to induce dimerization (Livnah et al, 1998, 1999 Remy et al, 1999 Wilson and JoUiffe, 1999). Based on patterns of cross-hormone and cross-species activities and the known structural differences in the active complexes, exact receptor orientation is probably not as crucial for prolactin and growth hormone systems, although this has not been directly established. 

Bernat, B., Pal, G., Sun, M., and Kossiakoff, A. A. (2003). Determination of the energetics governing the regulatory step in growth hormone-induced receptor homodimerization. Proc. Natl. Acad. Sci. USA 100(3), 952-957. 

Duquesnoy, P., Sobrier, M. L., Duriez, B., Dastot, F., Buchanan, C. R., Savage, M. O., Preece, M. A., Craescu, C. T., Blouquit, Y., and Goossens, M. et al. (1994). A single amino acid substitution in the exoplasmic domain of the human growth hormone (GH) receptor confers familial GH resistance (Laron syndrome) with positive GH-binding activity by abolishing receptor homodimerization. EMBO J. 13(6), 1386-1395. 

---