The retinal cGMP phosphodiesterase gamma-subunit - a chameleon.
Intrinsically disordered proteins (IDPs) represent an emerging class of proteins (or domains) that are characterized by a lack of ordered secondary and tertiary structure. This group of proteins has recently attracted tremendous interest primarily because of a unique feature: they can bind to different targets due to their structural plasticity, and thus fulfill diverse functions. The inhibitory gamma-subunit (PDEgamma) of retinal PDE6 is an intriguing IDP, of which unique protein properties are being uncovered. PDEgamma critically regulates the turn on as well as the turn off of visual signaling through alternate interactions with the PDE6 catalytic core, transducin, and the regulator of G protein signaling RGS9-1. The intrinsic disorder of PDEgamma does not compromise, but rather, optimizes its functionality. PDEgamma "curls up" when free in solution but "stretches out" when binding with the PDE6 catalytic core. Conformational changes of PDEgamma also likely occur in its C-terminal PDE6-binding region upon interacting with transducin during PDE6 activation. Growing evidence shows that PDEgamma is also a player in non-phototransduction pathways, suggesting additional protein targets. Thus, PDEgamma is highly likely to be adaptive in its structure and function, hence a "chameleon".
Guo
Lian-Wang
LW
Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA. lianwangguo@wisc.edu
Ruoho
Arnold E
AE
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000737:chemistry* / Q000378:metabolism*; D004789:Enzyme Activation; D005128:Eye Diseases / Q000201:enzymology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D015293:Transducin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; C464657:RGS9BP protein, human; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D015293:Transducin