Conformational Differences Among Solution Structures of the Type I[alpha], II[alpha], and II[beta] Protein Kinase A Regulatory Subunit Homodimers: Role of the Linker Regions
- HHMI
The regulatory (R) subunits of the cAMP-dependent protein kinase (protein kinase A or PKA) are multi-domain proteins responsible for conferring cAMP-dependence and localizing PKA to specific subcellular locations. There are four isoforms of the R subunit in mammals that are similar in molecular mass and domain organization, but clearly serve different biological functions. Although high-resolution structures are available for the cAMP-binding domains and dimerization/docking domains of two isoforms, there are no high-resolution structures of any of the intact R subunit homodimer isoforms. The results of small-angle X-ray scattering studies presented here indicate that the RI{alpha}, RII{alpha}, and RII{beta} homodimers differ markedly in overall shape, despite extensive sequence homology and similar molecular masses. The RII{alpha} and RII{beta} homodimers have very extended, rod-like shapes, whereas the RI{alpha} homodimer likely has a compact Y-shape. Based on a comparison of the R subunit sequences, we predict that the linker regions are the likely cause of these large differences in shape among the isoforms. In addition, we show that cAMP binding does not cause large conformational changes in type I{alpha} or II{alpha} R subunit homodimers, suggesting that the activation of PKA by cAMP involves only local conformational changes in the R subunits.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1008697
- Journal Information:
- J. Mol. Biol., Vol. 337, Issue (5) ; 2004; ISSN 0022-2836
- Country of Publication:
- United States
- Language:
- ENGLISH
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