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

@article{citeulike:2369238, abstract = {The retinal phosphodiesterase (PDE6) inhibitory {gamma}-subunit (PDE{gamma}) plays a central role in vertebrate phototransduction through alternate interactions with the catalytic {alpha}-subunits of PDE6 and the {alpha}-subunit of transducin ({alpha}t). Detailed structural analysis of PDE{gamma} has been hampered by its intrinsic disorder. We present here the NMR solution structure of PDE{gamma}, which reveals a loose fold with transient structural features resembling those seen previously in the x-ray structure of PDE{gamma}4687 when bound to {alpha}t in the transition-state complex. NMR mapping of the interaction between PDE{gamma}4687 and the chimeric PDE5/6 catalytic domain confirmed that C-terminal residues 7487 of PDE{gamma} 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 PDE{gamma} and {alpha}t during the phototransduction cascade involves the selection of preconfigured transient conformations. 10.1073/pnas.0709558105}, author = {Song, Jikui and Guo, Lian-Wang and Muradov, Hakim and Artemyev, Nikolai O. and Ruoho, Arnold E. and Markley, John L. }, citeulike-article-id = {2369238}, doi = {10.1073/pnas.0709558105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {clip2, experiment, intrinsic\_disorder, nmr}, month = {February}, number = {5}, pages = {1505--1510}, posted-at = {2008-02-13 10:31:56}, priority = {2}, title = {Intrinsically disordered {gamma}-subunit of cGMP phosphodiesterase encodes functionally relevant transient secondary and tertiary structure}, url = {http://dx.doi.org/10.1073/pnas.0709558105}, volume = {105}, year = {2008} }

TY - JOUR ID - citeulike:2369238 L3 - citeulike-article-id:2369238 TI - Intrinsically disordered {gamma}-subunit of cGMP phosphodiesterase encodes functionally relevant transient secondary and tertiary structure JF - Proceedings of the National Academy of Sciences VL - 105 IS - 5 SP - 1505 EP - 1510 N2 - The retinal phosphodiesterase (PDE6) inhibitory {gamma}-subunit (PDE{gamma}) plays a central role in vertebrate phototransduction through alternate interactions with the catalytic {alpha}-subunits of PDE6 and the {alpha}-subunit of transducin ({alpha}t). Detailed structural analysis of PDE{gamma} has been hampered by its intrinsic disorder. We present here the NMR solution structure of PDE{gamma}, which reveals a loose fold with transient structural features resembling those seen previously in the x-ray structure of PDE{gamma}4687 when bound to {alpha}t in the transition-state complex. NMR mapping of the interaction between PDE{gamma}4687 and the chimeric PDE5/6 catalytic domain confirmed that C-terminal residues 7487 of PDE{gamma} 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 PDE{gamma} and {alpha}t during the phototransduction cascade involves the selection of preconfigured transient conformations. 10.1073/pnas.0709558105 KW - clip2 KW - experiment KW - intrinsic_disorder KW - nmr AU - Song, Jikui AU - Guo, Lian-Wang AU - Muradov, Hakim AU - Artemyev, Nikolai AU - Ruoho, Arnold AU - Markley, John PY - 2008/02/05/ UR - http://dx.doi.org/10.1073/pnas.0709558105 ER -