title: Intrinsically disordered gamma-subunit of cGMP phosphodiesterase encodes functionally relevant transient secondary and tertiary structure.
abstract: The retinal phosphodiesterase (PDE6) inhibitory gamma-subunit (PDEgamma) plays a central role in vertebrate phototransduction through alternate interactions with the catalytic alphabeta-subunits of PDE6 and the alpha-subunit of transducin (alpha(t)). Detailed structural analysis of PDEgamma has been hampered by its intrinsic disorder. We present here the NMR solution structure of PDEgamma, which reveals a loose fold with transient structural features resembling those seen previously in the x-ray structure of PDEgamma(46-87) when bound to alpha(t) in the transition-state complex. NMR mapping of the interaction between PDEgamma(46-87) and the chimeric PDE5/6 catalytic domain confirmed that C-terminal residues 74-87 of PDEgamma are involved in the association and demonstrated that its W70 indole group, which is critical for subsequent binding to alpha(t), is left free at this stage. These results indicate that the interaction between PDEgamma and alpha(t) during the phototransduction cascade involves the selection of preconfigured transient conformations.
authors.affiliation: Center for Eukaryotic Structural Genomics, Department of Biochemistry, University of Wisconsin, Madison, WI 53706-1544, USA.
authors.forename: Jikui
authors.initials: J
authors.lastname: Song
authors.forename: Lian-Wang
authors.initials: LW
authors.lastname: Guo
authors.forename: Hakim
authors.initials: H
authors.lastname: Muradov
authors.forename: Nikolai O
authors.initials: NO
authors.lastname: Artemyev
authors.forename: Arnold E
authors.initials: AE
authors.lastname: Ruoho
authors.forename: John L
authors.initials: JL
authors.lastname: Markley
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000737:chemistry*; D006801:Humans; D051379:Mice; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits
chemical_list: D021122:Protein Subunits; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6