Work

Molecular Simulations Reveal an Unresolved Conformation of the Type IA Protein Kinase A Regulatory Subunit and Suggest Its Role in the cAMP Regulatory Mechanism

Year: 2017

Type: article

Abstract: We identify a previously unresolved, unrecognized, and highly stable conformation of the protein kinase A (PKA) regulatory subunit RIα. This conformation, which we term the "Flipback" structure, bridges conflicting characteristics in crystallographic structures and solution experiments of the PKA RIα heterotetramer. Our simulations reveal a hinge residue, G235, in the B/C helix that is conserved through all isoforms of RI. Brownian dynamics simulations suggest that the Flipback conformation plays a role in cAMP association to the A domain of the R subunit.

Source: Biochemistry

DOI: 10.1021/acs.biochem.7b00461

Authors: Sophia P. Hirakis, Robert D. Malmstrom, Rommie E. Amaro

Institution: University of California San Diego

Language: English

Topic: Protein Structure and Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences, National Institute of Biomedical Imaging and Bioengineering

Awards: A Structural Systems Biology Approach to Drug Discovery, Modeling and analysis of the mechanochemical processes that govern clathrin-mediated endocytosis, NATIONAL BIOMEDICAL COMPUTATION RESOURCE, Training in Multi-scale Analysis of Biological Structure and Function