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Engineering a protein scaffold from a PHD finger

Citation

Kwan, AH and Gell, DA and Verger, A and Crossley, M and Matthews, JM and Mackay, JP, Engineering a protein scaffold from a PHD finger, Structure, 11, (7) pp. 803-813. ISSN 0969-2126 (2003) [Refereed Article]

DOI: doi:10.1016/S0969-2126(03)00122-9

Abstract

The design of proteins with tailored functions remains a relatively elusive goal. Small size, a well-defined structure, and the ability to maintain structural integrity despite multiple mutations are all desirable properties for such designer proteins. Many zinc binding domains fit this description. We determined the structure of a PHD finger from the transcriptional cofactor Mi2β and investigated the suitability of this domain as a scaffold for presenting selected binding functions. The two flexible loops in the structure were mutated extensively by either substitution or expansion, without affecting the overall fold of the domain. A binding site for the corepressor CtBP2 was also grafted onto the domain, creating a new PHD domain that can specifically bind CtBP2 both in vitro and in the context of a eukaryotic cell nucleus. These results represent a step toward designing new regulatory proteins for modulating aberrant gene expression in vivo.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Structural Biology (incl. Macromolecular Modelling)
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Biological Sciences
Author:Gell, DA (Dr David Gell)
ID Code:64555
Year Published:2003
Web of Science® Times Cited:45
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-08-12
Last Modified:2011-08-01
Downloads:0

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