Technology Insight: modern methods to monitor protein-protein interactions reveal functional TSH receptor oligomerization.
The formation of supramolecular structures (dimers or oligomers) is emerging as an important aspect of G-protein-coupled receptor (GPCR) biology. In some cases, GPCR oligomerization is a prerequisite for membrane targeting or function; in others, the relevance of the phenomenon is presently unknown. Although supramolecular structures of GPCRs were initially documented by classical biochemical techniques such as coimmunoprecipitation, many recent advances in the field of GPCR oligomerization have been prompted by the introduction of two new biophysical assays based on Förster's resonance energy transfer-fluorescence resonance energy transfer and bioluminescence resonance energy transfer. These modern techniques allow the study of protein-protein interaction in intact cells, and can be used to monitor monomer association and dissociation in vivo. Recently, oligomerization has also been reported in the case of the TSH receptor (TSHR). This review will focus on the previously unsuspected implications that oligomerization has in TSHR physiology and pathology. It is now clear that TSHR oligomerization is constitutive, occurs early during post-translational processing, and may be involved in membrane targeting and activation by the hormone or by stimulating antibodies. Oligomerization between inactive mutants and wild-type TSHR provides a molecular explanation for the dominant forms of TSH resistance.
Persani
Luca
L
Department of Medical Sciences, University of Milan, Milan, Italy. luca.persani@unimi.it
Calebiro
Davide
D
Bonomi
Marco
M
D019281:Dimerization; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods*; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D009490:Neurosecretory Systems / Q000378:metabolism; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D011989:Receptors, Thyrotropin / Q000378:metabolism*; D018382:Thyroid Hormone Resistance Syndrome / Q000378:metabolism
D008164:Luminescent Proteins; D043562:Receptors, G-Protein-Coupled; D011989:Receptors, Thyrotropin