Defective internal allosteric network imparts dysfunctional ATP/substrate-binding cooperativity in oncogenic chimera of protein kinase A

Cristina Olivieri; Caitlin Walker; Adak Karamafrooz; Yingjie Wang; V. S. Manu; Fernando Porcelli; Donald K. Blumenthal; David D. Thomas; David A. Bernlohr; Simon M. Sandford; Susan S. Taylor; Gianluigi Veglia

doi:10.1038/s42003-021-01819-6

Communications Biology (Mar 2021)

Defective internal allosteric network imparts dysfunctional ATP/substrate-binding cooperativity in oncogenic chimera of protein kinase A

Cristina Olivieri,
Caitlin Walker,
Adak Karamafrooz,
Yingjie Wang,
V. S. Manu,
Fernando Porcelli,
Donald K. Blumenthal,
David D. Thomas,
David A. Bernlohr,
Simon M. Sandford,
Susan S. Taylor,
Gianluigi Veglia

Affiliations

Cristina Olivieri: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota
Caitlin Walker: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota
Adak Karamafrooz: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota
Yingjie Wang: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota
V. S. Manu: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota
Fernando Porcelli: DIBAF - University of Tuscia – Largo dell’ Università
Donald K. Blumenthal: Department of Pharmacology and Toxicology, University of Utah
David D. Thomas: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota
David A. Bernlohr: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota
Simon M. Sandford: Laboratory of Cellular Biophysics, Rockefeller University
Susan S. Taylor: Department of Chemistry and Biochemistry and Pharmacology, University of California at San Diego
Gianluigi Veglia: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota

DOI: https://doi.org/10.1038/s42003-021-01819-6
Journal volume & issue: Vol. 4, no. 1
pp. 1 – 11

Abstract

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Olivieri, Walker, Karamafrooz et al. show that the fusion of the dynamic J-domain to PKA-C (PKA-CDNAJB1) disrupts the internal allosteric network, attenuating the nucleotide/PKI binding cooperativity. This study suggests that the reduced allosteric cooperativity may contribute to the pathology that PKA-CDNAJB1 drives.

Published in Communications Biology

ISSN: 2399-3642 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science: Biology (General)
Website: https://www.nature.com/commsbio/

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