Conformationally dynamic C helix of the RIalpha subunit of protein kinase A mediates isoform-specific domain reorganization upon C subunit binding.

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Publication Type Journal Article
School or College College of Pharmacy; College of Science; School of Medicine
Department Chemistry; Biochemistry; Biomedical Informatics; Pharmacology & Toxicology
Creator Blumenthal, Donald K.; Trewhella, Jill
Other Author Vigil, Dominico; Taylor, Susan S.
Title Conformationally dynamic C helix of the RIalpha subunit of protein kinase A mediates isoform-specific domain reorganization upon C subunit binding.
Date 2005-10-21
Description Different isoforms of the full-length protein kinase A (PKA) regulatory subunit homodimer (R2) and the catalytic (C) subunit-bound holoenzyme (R2C2) have very different global structures despite similar molecular weights and domain organization within their primary sequences. To date, it has been the linker sequence between the R subunit dimerization/docking domain and cAMP-binding domain A that has been implicated in modulating domain interactions to give rise to these differences in global structure. The small angle solution scattering data presented here for three different isoforms of PKA heterodimer (deltaR-C) complexes reveal a role for another conformationally dynamic sequence in modulating inter-subunit and domain interactions, the C helix that connects the cAMP-binding domains A and B of the R subunit. The deltaR-C heterodimer complexes studied here were each formed with a monomeric N-terminal deletion mutant of the R subunit (deltaR) that contains the inhibitor sequence and both cAMP-binding domains. The scattering data show that type IIalpha and type IIbeta deltaR-C heterodimers are relatively compact and globular, with the C subunit contacting the inhibitor sequence and both cAMP-binding domains. In contrast, the type Ialpha heterodimer is significantly more extended, with the C subunit interacting with the inhibitor sequence and cAMP-binding domain A, whereas domain B extends out such that its surface is almost completely solvent exposed. These data implicate the C helix of RIalpha in modulating isoform-specific interdomain communication in the PKA holoenzyme, adding another layer of structural complexity to our understanding of signaling dynamics in this multisubunit, multidomain protein kinase.
Type Text
Publisher American Society for Biochemistry and Molecular Biology (ASBMB)
Volume 280
Issue 42
First Page 35521
Last Page 35527
Subject Protein Isoforms; Global Structures; cAMP
Subject MESH Catalytic Domain; Cyclic AMP-Dependent Protein Kinases; Dimerization; Escherichia coli; Gene Deletion; Mutation; Protein Conformation; Recombinant Proteins; Scattering, Radiation
Language eng
Bibliographic Citation Vigil D, Blumenthal DK, Taylor SS, Trewhella J. The conformationally dynamic C helix of the RIalpha subunit of protein kinase A mediates isoform-specific domain reorganization upon C subunit binding. J Biol Chem. 2005 Oct 21;280(42):35521-7. Epub 2005 Aug 17. Retrieved September 15,2006 from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=Display&DB=pubmed
Rights Management Copyright © American Society for Biochemistry and Molecular Biology, J Biol Chem., 280, 35521-35527, 2005
Format Medium application/pdf
ARK ark:/87278/s6kh15ds
Setname ir_uspace
Date Created 2012-06-13
Date Modified 2012-06-13
ID 702500
Reference URL https://collections.lib.utah.edu/ark:/87278/s6kh15ds
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