STRUCTURAL DETERMINATION OF R9AP ? THE RGS ANCHORING PROTEIN

University Of Wisconsin-Madison, Madison WI

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Regulators of G protein signaling (RGS) are ubiquitous signaling molecules that critically regulate cellular responses mediated by G protein-coupled receptor (GPCR) pathways. Most RGS proteins act by stimulating the rate of the GTP hydrolysis of the [unreadable] subunits of G proteins (G[unreadable]), thus speeding up their inactivation and limiting the duration of GPCR signaling. R9AP (RGS9 Anchoring Protein) participates regulation of visual signaling by interacting with RGS9. Three major functions have been attributed to R9AP: tethering RGS9 to the photoreceptor disc membrane, enhancing the GTPase stimulating activity of RGS9, and modulating RGS9 expression levels. Since the R9AP cytosolic domain of ~ 15 kDa can be readily expressed and purified from E. coli, we have set out to determine its solution structure through NMR. Given that R9AP is a homolog to another RGS binding protein, R7BP, which plays important celluar roles by interacting with a variety of R7 family RGS proteins, an atomic structure of R9AP is expected to afford critical insights into the RGS regulatory mechanisms of an array of cell signaling pathways.