Homodimerization Heterodimerization

Another reagent that has found use in pinacolic coupling is prepared from VC13 and zinc dust.264 This reagent is selective for aldehydes that can form chelated intermediates, such as (3-formylamides, a-amidoaldehydes, a-phosphinoylaldehydes,265 and 8-ketoaldehydes.266 The vanadium reagent can be used for both homodimerization and heterodimerization. In the latter case, the reactive aldehyde is added to an excess of the second aldehyde. Under these conditions, the ketyl intermediate formed from the chelated aldehyde reacts with the second aldehyde. 

In addition to the key importance of the homodimerization for mGluR function, two cases of heterodimerization (or heterooligomerization) between mGluRs and other GPCRs have been reported recently. 

The GPCR C-terminal region, with or without a coiled-coil motif, has been implicated in the heterodimerization process of GABAb(1)-GABAb(2) (78,80), as well as in the homodimerization of 5-opioid receptor (120). However, the possibility cannot be ruled out that the indirect evidence for the involvement of the C-terminal domain results from changes produced by the deletion of the C-terminal tail, that alters the conformation of the receptors and causes decreased interactions between transmembrane helices and oligomer disruption. 

Figure 17.8 Ribbon diagrams of the heterodimeric MoFe-protein (left) and homodimeric Fe-proteins of nitrogenase (right). The a- and P-subunits to the left of the MoFe-protein are shown in light and dark shading, respectively, while the metalloclusters are shown as dark space-filling models on the right side. The two subunits of the Fe-protein are shown in light and dark shading, with the 4Fe-4S cluster at the dimer interface as a space-filling model. (From Rees et al., 2005. Reproduced with permission of the Royal Society.)...

Fig. 2. Representative examples of recent generation of synthetic quinine-based and/or quinidine-based homodimeric and heterodimeric derivatives.

Dong H, Hartgerink JD. Short homodimeric and heterodimeric coiled coils. Biomacromolecules 2006 7 691-695. 

The phosphorylated Stat proteins form homodimeric or heterodimeric complexes and are transported as such into the nucleus (Fig. 11.7). In the nucleus, they bind to corresponding DNA elements in the promoter region of cytokine responsive genes. Stimulation of transcription takes place in cooperation with other proteins such as p300, CBP (see 1.4.6), glucocorticoid receptors and c-jim. 

To see whether water could be activated and added to Jt-systems other than alkynes, the metal-catalyzed hydrolysis of nitriles was studied [20]. For this purpose novel homodimeric and heterodimeric bis(acetylacetonato)ruthenium(ii) complexes bearing the 6-diphenylphosphino-N-pivaloyl-2-aminopyridine (10a) and 3-diphenylphosphinoisoquinolone (Ila) ligands were prepared. The molecular structures of these precatalyst were studied in solution and also in the solid state and revealed some unusual hydrogen-bonding patterns, in particular for the heterodimeric system in which the acetylacetonato ligand is involved (Scheme 2.7). 

Deloulme JC, Gentil BJ, Baudier J. 2003. Monitoring of S100 homodimerization and heterodimeric interactions by the yeast two-hybrid system. Microsc Res Tech 60(6) 560-568. 

In contrast to the steroid receptor family, members of the thyroid receptor family typically do not associate with accessory proteins and are not localized to the extranucleus matrix. Rather, these receptors exist in the basal state associated with chromatin in the cell nucleus. When bound by hormone ligand, thyroid receptor family members dissociate from the chromatin and typically form heterodimeric combinations with the retinoid-X receptor (RXR). RXR also is capable of homodimerization in association with its ligand 9-cis retinoic acid. Thus high 9-cis retinoic acid levels apparently promote homodimerization, and low levels are permissive of heterodimerization of RXR with activation by the partner ligand. 

Fig. 9 A Calix[4]arene tetraurea dimeric capsules with a particular head-to-tail hydrogen bond network. B Achiral tetraurea units form achiral homodimeric capsules, while C two different achiral units forms chiral heterodimeric capsules...

The hormone-receptor complexes interact pairwise with DNA. These pairs (dimers) may consist of two identical hormone-receptor complexes (homodimeric form, e.g., with adrenal or gonadal hormones). The thyroid hormone-receptor complex occurs in heterodimeric form and combines with a cis-retinoic acid-receptor complex. 

The members of the cytosolic hormone receptor family are homologous proteins and the mechanism of action involves translocation of the receptor with hormone bound to the nucleus, where it homodimerizes (or heterodimerizes with related activated receptors) and binds to specific promoters to switch on transcription of particular genes. The ultimate response to the hormonal stimulus is expression of particular proteins that variously influence development and metabolism as briefly outlined below. 

---