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 γ-subunit (PDEγ) of retinal PDE6 is an intriguing IDP, of which unique protein properties are being uncovered. PDEγ 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 PDEγ does not compromise, but rather, optimizes its functionality. PDEγ “curls up” when free in solution but “stretches out” when binding with the PDE6 catalytic core. Conformational changes of PDEγ also likely occur in its Cterminal PDE6-binding region upon interacting with transducin during PDE6 activation. Growing evidence shows that PDEγ is also a player in non-phototransduction pathways, suggesting additional protein targets. Thus, PDE?? is highly likely to be adaptive in its structure and function, hence a “chameleon”.
Keywords: PDEγ, phototransduction, NMR, conformational selection, intrinsically disordered proteins, protein-protein interaction, non-visual function, eye diseases
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