Structure of a PKA RIα Recurrent Acrodysostosis Mutant Explains Defective cAMP-Dependent Activation

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• 作者：Jessica GH Bruystens¹ ; Jian Wu¹ ; ² ; Audrey Fortezzo¹ ; Jason Del Rio² ; Cole Nielsen² ; Donald K. Blumenthal³ ; Ruth Rock⁴ ; Eduard Stefan⁴ ; Susan S. Taylor¹ ; ² ; ^{staylor@ucsd.edu}
• 关键词：PKA ; cAMP protein kinase A ; CNC ; Carney complex ; ACRDYS ; acrodysostosis ; CNB ; cAMP-binding ; R ; regulatory ; C ; catalytic ; IS ; inhibitor site ; PBC ; phosphate-binding cassette ; NMD ; nonsense-mediated mRNA decay ; SAXS ; small angle X-ray scattering ; FP ; fluorescence polarization ; PCA ; protein-fragment complementation assay ; Rluc ; Renilla Luciferase ; PPI ; protein ; protein interaction ; β2AR ; beta-2 adrenergic receptor ; G-loop ; glycine-rich loop
• 刊名：Journal of Molecular Biology
• 出版年：2016
• 出版时间：4 December 2016
• 年：2016
• 卷：428
• 期：24
• 页码：4890-4904
• 全文大小：2396 K
• 卷排序：428

文摘

PKA, ubiquitous in mammalian cells, controls many biological processes, and RIa is a major target for diseases associated with PKA signaling. Nonsense-mediated mRNA decay as well as disease mutations in RIα highlight the importance of this holoenzyme for regulating PKA signaling. Mapping these disease mutations reveals clustering at functional hot-spots that define either gain-of-function (CNC) or loss-of-function (ACRDYS) phenotypes. Crystal structure describes one of the dysfunctional ACRDYS mutants with a C-terminal deletion.