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

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...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Publishing Group 2021-03-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-021-01819-6
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spelling doaj-43c1fcd3a0854b83a040ab4779192c9e2021-03-11T12:04:34ZengNature Publishing GroupCommunications Biology2399-36422021-03-014111110.1038/s42003-021-01819-6Defective internal allosteric network imparts dysfunctional ATP/substrate-binding cooperativity in oncogenic chimera of protein kinase ACristina Olivieri0Caitlin Walker1Adak Karamafrooz2Yingjie Wang3V. S. Manu4Fernando Porcelli5Donald K. Blumenthal6David D. Thomas7David A. Bernlohr8Simon M. Sandford9Susan S. Taylor10Gianluigi Veglia11Department of Biochemistry, Molecular Biology, and Biophysics, University of MinnesotaDepartment of Biochemistry, Molecular Biology, and Biophysics, University of MinnesotaDepartment of Biochemistry, Molecular Biology, and Biophysics, University of MinnesotaDepartment of Biochemistry, Molecular Biology, and Biophysics, University of MinnesotaDepartment of Biochemistry, Molecular Biology, and Biophysics, University of MinnesotaDIBAF - University of Tuscia – Largo dell’ UniversitàDepartment of Pharmacology and Toxicology, University of UtahDepartment of Biochemistry, Molecular Biology, and Biophysics, University of MinnesotaDepartment of Biochemistry, Molecular Biology, and Biophysics, University of MinnesotaLaboratory of Cellular Biophysics, Rockefeller UniversityDepartment of Chemistry and Biochemistry and Pharmacology, University of California at San DiegoDepartment of Biochemistry, Molecular Biology, and Biophysics, University of MinnesotaOlivieri, 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.https://doi.org/10.1038/s42003-021-01819-6
collection DOAJ
language English
format Article
sources DOAJ
author 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
spellingShingle 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
Defective internal allosteric network imparts dysfunctional ATP/substrate-binding cooperativity in oncogenic chimera of protein kinase A
Communications Biology
author_facet 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
author_sort Cristina Olivieri
title Defective internal allosteric network imparts dysfunctional ATP/substrate-binding cooperativity in oncogenic chimera of protein kinase A
title_short Defective internal allosteric network imparts dysfunctional ATP/substrate-binding cooperativity in oncogenic chimera of protein kinase A
title_full Defective internal allosteric network imparts dysfunctional ATP/substrate-binding cooperativity in oncogenic chimera of protein kinase A
title_fullStr Defective internal allosteric network imparts dysfunctional ATP/substrate-binding cooperativity in oncogenic chimera of protein kinase A
title_full_unstemmed Defective internal allosteric network imparts dysfunctional ATP/substrate-binding cooperativity in oncogenic chimera of protein kinase A
title_sort defective internal allosteric network imparts dysfunctional atp/substrate-binding cooperativity in oncogenic chimera of protein kinase a
publisher Nature Publishing Group
series Communications Biology
issn 2399-3642
publishDate 2021-03-01
description 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.
url https://doi.org/10.1038/s42003-021-01819-6
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