TY - JOUR
T1 - Surface sites for engineering allosteric control in proteins
AU - Lee, Jeeyeon
AU - Natarajan, Madhusudan
AU - Nashine, Vishal C.
AU - Socolich, Michael
AU - Vo, Tina
AU - Russ, William P.
AU - Benkovic, Stephen J.
AU - Ranganathan, Rama
PY - 2008/10/17
Y1 - 2008/10/17
N2 - Statistical analyses of protein families reveal networks of coevolving amino acids that functionally link distantly positioned functional surfaces. Such linkages suggest a concept for engineering allosteric control into proteins: The intramolecular networks of two proteins could be joined across their surface sites such that the activity of one protein might control the activity of the other. We tested this idea by creating PAS-DHFR, a designed chimeric protein that connects a light-sensing signaling domain from a plant member of the Per/Arnt/Sim (PAS) family of proteins with Escherichia coli dihydrofolate reductase (DHFR). With no optimization, PAS-DHFR exhibited light-dependent catalytic activity that depended on the site of connection and on known signaling mechanisms in both proteins. PAS-DHFR serves as a proof of concept for engineering regulatory activities into proteins through interface design at conserved allosteric sites.
AB - Statistical analyses of protein families reveal networks of coevolving amino acids that functionally link distantly positioned functional surfaces. Such linkages suggest a concept for engineering allosteric control into proteins: The intramolecular networks of two proteins could be joined across their surface sites such that the activity of one protein might control the activity of the other. We tested this idea by creating PAS-DHFR, a designed chimeric protein that connects a light-sensing signaling domain from a plant member of the Per/Arnt/Sim (PAS) family of proteins with Escherichia coli dihydrofolate reductase (DHFR). With no optimization, PAS-DHFR exhibited light-dependent catalytic activity that depended on the site of connection and on known signaling mechanisms in both proteins. PAS-DHFR serves as a proof of concept for engineering regulatory activities into proteins through interface design at conserved allosteric sites.
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U2 - 10.1126/science.1159052
DO - 10.1126/science.1159052
M3 - Article
C2 - 18927392
AN - SCOPUS:54249105941
SN - 0036-8075
VL - 322
SP - 438
EP - 442
JO - Science
JF - Science
IS - 5900
ER -