Allosteric pluripotency arises when the functional response of an allosteric receptor to an allosteric stimulus depends on additional allosteric modulators. Here, we discuss allosteric pluripotency as observed in the prototypical Protein Kinase A (PKA) as well as in other signaling systems, from typical multidomain signaling proteins to bacterial enzymes. We identify key drivers of pluripotent allostery and illustrate how hypothesizing allosteric pluripotency may solve apparent discrepancies currently present in the literature regarding the dual nature of known allosteric modulators. We also outline the implications of allosteric pluripotency for cellular signaling and allosteric drug design, and analyze the challenges and opportunities opened by the pluripotent nature of allostery.
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April 2022
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Immunofluorescence staining of mouse hepatocytes cultured for 24 h with anti-α1-antitrypsin and anti-calreticulin antibodies.
Review Article|
April 11 2022
Allosteric pluripotency: challenges and opportunities
Madoka Akimoto;
Madoka Akimoto
1Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada
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Karla Martinez Pomier;
Karla Martinez Pomier
1Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada
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Bryan VanSchouwen;
Bryan VanSchouwen
1Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada
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Jung Ah Byun;
Jung Ah Byun
1Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada
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Mariia Khamina;
Mariia Khamina
1Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada
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Giuseppe Melacini
1Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada
2Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada
Correspondence: Giuseppe Melacini (melacin@mcmaster.ca)
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Publisher: Portland Press Ltd
Received:
November 21 2021
Revision Received:
March 17 2022
Accepted:
March 21 2022
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2022
Biochem J (2022) 479 (7): 825–838.
Article history
Received:
November 21 2021
Revision Received:
March 17 2022
Accepted:
March 21 2022
Citation
Madoka Akimoto, Karla Martinez Pomier, Bryan VanSchouwen, Jung Ah Byun, Mariia Khamina, Giuseppe Melacini; Allosteric pluripotency: challenges and opportunities. Biochem J 14 April 2022; 479 (7): 825–838. doi: https://doi.org/10.1042/BCJ20210528
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