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Combinatorial Control through Allostery

Galstyan, Vahe and Funk, Luke and Einav, Tal and Phillips, Rob (2019) Combinatorial Control through Allostery. Journal of Physical Chemistry B, 123 (13). pp. 2792-2800. ISSN 1520-6106. PMCID PMC6467274. http://resolver.caltech.edu/CaltechAUTHORS:20190102-135256302

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Abstract

Many instances of cellular signaling and transcriptional regulation involve switch-like molecular responses to the presence or absence of input ligands. To understand how these responses come about and how they can be harnessed, we develop a statistical mechanical model to characterize the types of Boolean logic that can arise from allosteric molecules following the Monod–Wyman–Changeux (MWC) model. Building upon previous work, we show how an allosteric molecule regulated by two inputs can elicit AND, OR, NAND, and NOR responses but is unable to realize XOR or XNOR gates. Next, we demonstrate the ability of an MWC molecule to perform ratiometric sensing—a response behavior where activity depends monotonically on the ratio of ligand concentrations. We then extend our analysis to more general schemes of combinatorial control involving either additional binding sites for the two ligands or an additional third ligand and show how these additions can cause a switch in the logic behavior of the molecule. Overall, our results demonstrate the wide variety of control schemes that biological systems can implement using simple mechanisms.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/acs.jpcb.8b12517DOIArticle
https://pubs.acs.org/doi/suppl/10.1021/acs.jpcb.8b12517PublisherSupporting Information
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467274PubMed CentralArticle
https://doi.org/10.1101/508226DOIDiscussion Paper
ORCID:
AuthorORCID
Galstyan, Vahe0000-0001-7073-9175
Einav, Tal0000-0003-0777-1193
Phillips, Rob0000-0003-3082-2809
Additional Information:© 2019 American Chemical Society. Received: December 28, 2018; Revised: February 5, 2019; Published: February 15, 2019. It is a great pleasure to acknowledge the contributions of Bill Eaton to our understanding of allostery. We thank Chandana Gopalakrishnappa and Parijat Sil for their input on this work, and Michael Elowitz for his insights and valuable feedback on the manuscript. This research was supported by La Fondation Pierre-Gilles de Gennes, the Rosen Center at Caltech, the Department of Defense through the National Defense Science & Engineering Graduate Fellowship (NDSEG) Program (LF), and the National Institutes of Health DP1 OD000217 (Director’s Pioneer Award), R01 GM085286, and 1R35 GM118043-01 (MIRA). We are grateful to the Burroughs Wellcome Fund for its support of the Physical Biology of the Cell Course at the Marine Biological Laboratory, where part of this work was completed. Author Contributions: V.G. and L.F. contributed equally to this work. The authors declare no competing financial interest.
Group:Rosen Bioengineering Center
Funders:
Funding AgencyGrant Number
La Fondation Pierre-Gilles de GennesUNSPECIFIED
Donna and Benjamin M. Rosen Bioengineering CenterUNSPECIFIED
National Defense Science and Engineering Graduate (NDSEG) FellowshipUNSPECIFIED
NIHDP1 OD000217
NIHR01 GM085286
NIH1R35 GM118043-01
Burroughs-Wellcome FundUNSPECIFIED
PubMed Central ID:PMC6467274
Record Number:CaltechAUTHORS:20190102-135256302
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20190102-135256302
Official Citation:Combinatorial Control through Allostery. Vahe Galstyan, Luke Funk, Tal Einav, and Rob Phillips. The Journal of Physical Chemistry B 2019 123 (13), 2792-2800 DOI: 10.1021/acs.jpcb.8b12517
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:91986
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:03 Jan 2019 15:24
Last Modified:15 May 2019 16:26

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