Complexes between photoactivated rhodopsin and transducin: progress and questions.
Activation of GPCRs (G-protein-coupled receptors) leads to conformational changes that ultimately initiate signal transduction. Activated GPCRs transiently combine with and activate heterotrimeric G-proteins resulting in GTP replacement of GDP on the G-protein alpha subunit. Both the detailed structural changes essential for productive GDP/GTP exchange on the G-protein alpha subunit and the structure of the GPCR-G-protein complex itself have yet to be elucidated. Nevertheless, transient GPCR-G-protein complexes can be trapped by nucleotide depletion, yielding an empty-nucleotide G-protein-GPCR complex that can be isolated. Whereas early biochemical studies indicated formation of a complex between G-protein and activated receptor only, more recent results suggest that G-protein can bind to pre-activated states of receptor or even couple transiently to non-activated receptor to facilitate rapid responses to stimuli. Efficient and reproducible formation of physiologically relevant, conformationally homogenous GPCR-G-protein complexes is a prerequisite for structural studies designed to address these possibilities.
Jastrzebska
Beata
B
Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4965, USA. bxj27@case.edu
Tsybovsky
Yaroslav
Y
Palczewski
Krzysztof
K
D000818:Animals; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry; D006801:Humans; D008954:Models, Biological; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry; D012243:Rhodopsin / Q000737:chemistry*; D015398:Signal Transduction; D015293:Transducin / Q000737:chemistry*
D043562:Receptors, G-Protein-Coupled; D012243:Rhodopsin; D020962:Heterotrimeric GTP-Binding Proteins; D015293:Transducin