Ligand dimeric receptor state

As previously noted, the LBD of the receptor presents a series of functions that are not very well delimited such as those of dimerization with another receptor, nuclear translocation, and activation of the ligand-dependent gene transcription. As was just mentioned, the interaction of a ligand with its receptor has as its immediate consequence the conformational change of the molecule, a change that also determines the molecule s functionality. The importance of this point is that the stated conformational change is predetermined by the chemical nature of the ligand and the form in which it interacts with the receptor. 

The contributors to this volume have shown how far our understanding of the molecular mechanisms of G protein signaling has come, but also how much remains to be discovered. What is the chemo-mechanical mechanism of G protein activation by receptors What are the relevant states of receptors how are they differentially stabilized by ligands what is the functional role of receptor dimerization in the modulation and control of G protein activation, or the coordination of other signaling functions. Do G protein signalosomes exist If so, what (in addition to the obvious ) are their components how tightly are they integrated—kinetically and structurally—and how and where are they assembled at the plasma... 

Figure 17.4 Intracellular steroid receptor activation by hormone ligands, (a) Steroid hormones diffuse across the cell membrane into the cell. (b) Steroid hormone receptors in the basal state bound to accessory proteins, (c) Steroid hormones bind to receptors and accessory proteins are dissociated from the receptors. (d) Hormone receptor complexes dimerize. (e) Dimer complexes enter the nucleus and initiate transcription of responsive genes.

The chemotaxis receptors that do not bind chemokines also form dimers under certain conditions, but have not yet been found to undergo ligand-induced changes in oligomeric state. The G5a receptor is proposed to constitutively dimerize by association of respective TMIV domains, or possibly an interaction between TMl and TMII (Klco et at, 2003). For this receptor, no evidence yet exists to support ligand-induced dimerization... 

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