Cooperativity (homotropic allostery) is the primary mechanism by which evolution steepens the binding curves of biomolecular receptors to produce more responsive input-output behavior in biomolecular systems. Motivated by the ubiquity with which nature employs this effect, over the past 15 years we, together with other groups, have engineered this mechanism into several otherwise noncooperative receptors. These efforts largely aimed to improve the utility of such receptors in artificial biotechnologies, such as synthetic biology and biosensors, but they have also provided the first quantitative, experimental tests of longstanding ideas about the mechanisms underlying cooperativity. In this article, we review the literature on the design of this effect, paying particular attention to the design strategies involved, the extent to which each can be rationally applied to (and optimized for) new receptors, and what each teaches us about the origins and optimization of this important phenomenon.

Ortega, G., Chamorro-Garcia, A., Ricci, F., Plaxco, K.w. (2023). On the rational design of cooperative receptors. ANNUAL REVIEW OF BIOPHYSICS, 52(1), 319-337 [10.1146/annurev-biophys-091222-082247].

On the rational design of cooperative receptors

Chamorro-Garcia, Alejandro;Ricci, Francesco;
2023-05-09

Abstract

Cooperativity (homotropic allostery) is the primary mechanism by which evolution steepens the binding curves of biomolecular receptors to produce more responsive input-output behavior in biomolecular systems. Motivated by the ubiquity with which nature employs this effect, over the past 15 years we, together with other groups, have engineered this mechanism into several otherwise noncooperative receptors. These efforts largely aimed to improve the utility of such receptors in artificial biotechnologies, such as synthetic biology and biosensors, but they have also provided the first quantitative, experimental tests of longstanding ideas about the mechanisms underlying cooperativity. In this article, we review the literature on the design of this effect, paying particular attention to the design strategies involved, the extent to which each can be rationally applied to (and optimized for) new receptors, and what each teaches us about the origins and optimization of this important phenomenon.
9-mag-2023
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore CHIM/01 - CHIMICA ANALITICA
Settore BIO/10 - BIOCHIMICA
English
allosterism; aptamers; binding-induced folding; bioengineering; biosensors; population shift; synthetic biology
Ortega, G., Chamorro-Garcia, A., Ricci, F., Plaxco, K.w. (2023). On the rational design of cooperative receptors. ANNUAL REVIEW OF BIOPHYSICS, 52(1), 319-337 [10.1146/annurev-biophys-091222-082247].
Ortega, G; Chamorro-Garcia, A; Ricci, F; Plaxco, Kw
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/323281
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