Intrinsically disordered [gamma]-subunit of cGMP phosphodiesterase encodes functionally relevant transient secondary and tertiary structure

The retinal phosphodiesterase (PDE6) inhibitory [gamma]-subunit (PD[E.sub.[gamma]],) plays a central role in vertebrate phototransduction through alternate interactions with the catalytic [alpha][beta]-subunits of PDE6 and the [alpha]-subunit of transducin ([[alpha].sub.t]). Detailed structural analysis of PD[E.sub.[gamma]] has been hampered by its intrinsic disorder. We present here the NMR solution structure of PD[E.sub.[gamma]], which reveals a loose fold with transient structural features resembling those seen previously in the x-ray structure of PD[E.sub.[gamma]46-87] when bound to at in the transitionstate complex. NMR mapping of the interaction between PD[E.sub.[gamma]46-87] and the chimeric PDE5/6 catalytic domain confirmed that Cterminal residues 74-87 of PD[E.sub.[gamma]] are involved in the association and demonstrated that its W70 indole group, which is critical for subsequent binding to at, is left free at this stage. These results indicate that the interaction between PD[E.sub.[gamma]] and [[alpha].sub.t] during the phototransduction cascade involves the selection of preconfigured transient conformations. NMR spectroscopy | protein recognition | transient structure | visual transduction