Design of protein switches based on an ensemble model of allostery

Jay H. Choi, Abigail H. Laurent, Vincent J. Hilser and Marc Ostermeier ()
Additional contact information
Jay H. Choi: Johns Hopkins University
Abigail H. Laurent: Johns Hopkins University
Vincent J. Hilser: Johns Hopkins University
Marc Ostermeier: Johns Hopkins University

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: Abstract Switchable proteins that can be regulated through exogenous or endogenous inputs have a broad range of biotechnological and biomedical applications. Here we describe the design of switchable enzymes based on an ensemble allosteric model. First, we insert an enzyme domain into an effector-binding domain such that both domains remain functionally intact. Second, we induce the fusion to behave as a switch through the introduction of conditional conformational flexibility designed to increase the conformational entropy of the enzyme domain in a temperature- or pH-dependent fashion. We confirm the switching behaviour in vitro and in vivo. Structural and thermodynamic studies support the hypothesis that switching result from an increase in conformational entropy of the enzyme domain in the absence of effector. These results support the ensemble model of allostery and embody a strategy for the design of protein switches.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/ncomms7968 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7968

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms7968

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().