GPCR oligomerization

This is completely analogous to the difference in oxygen binding between myoglobin and hemoglobin, and you may want to consult your biochemstry textbook for a refresher on the theory. 

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Maurel, D., Comps-Agrar, L., Brock, C., Rives, M. L., Bourrier, E., Ayoub, M. A., Bazin, H., Tinel, N., Durroux, T. Prezeau, L. et al. (2008). Cell-surface protein-protein interaction analysis with time-resolved FRET and snap-tag technologies Application to GPCR oligomerization. Nat. Methods J, 561-7. 

In the following paragraphs we summarize the current opinion on GPCR oligomerization and provide the details of the accumulated experimental and computational data on GPCR-GPCR interactions. 

The earlier computational studies (151,152,175,184,185) considered both domain-swapped and contact dimers as equally possible mechanisms of GPCR oligomerization. In contrast, the later computational studies on GPCR oligomerization (186-189) take into account only the hypothesis of contact dimers, supported by the more recent experimental evidence. For the prediction of heterodimer interfaces, the recent studies use a modified CMA methodology, termed subtractive correlated mutation (SCM) analysis (187,188). A similar method for the identification of physically interacting protein pairs has recently been reported in the literature (180). 

The reported data predate the observation of GPCR oligomerization, so the authors are not to be faulted for their interpretation. 

Heterologous expression systems are the preferred, and in some cases obligate models for stndy of GPCR oligomerization, although high expression levels can lead to nonspecific interactions. 

Key Words Chemokines oligomerization GPCR GAGs heparin crystallography NMR structure. 

Numerous examples of both ligand-induced [98,100-111] and ligand-independent (constitutive) oligomerization [79-81,86,94,96,97,106,112-130] have been reported in the literature over the last few years. However, inferences from these studies have not yet allowed a definitive conclusion about constitutive (i.e., GPCRs exist as stable preformed dimers) or ligand-induced oligomerization. 

Extracellular, transmembrane (TM), and/or C-terminal regions have been suggested to be involved in the oligomerization process of GPCRs. 

The Prediction of Likely Interfaces of Oligomerization Between TM Regions of GPCRs... 

Keywords Rhodopsin GPCR membrane proteins dimerization oligomerization G protein arrestin ... 

The recent explosion of number of papers on GPCR dimerization is summarized in several reviews.81112 This chapter is devoted to briefly show importance of oligomerization of GPCRs, current state of knowledge in this area and potential applications. 

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