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Engineering a protein scaffold from a PHD finger

journal contribution
posted on 2023-05-17, 02:59 authored by Kwan, AH, David GellDavid Gell, Verger, A, Crossley, M, Matthews, JM, Mackay, JP
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.

History

Publication title

Structure

Volume

11

Issue

7

Pagination

803-813

ISSN

0969-2126

Department/School

Menzies Institute for Medical Research

Publisher

Cell Press

Place of publication

1100 Massachusetts Ave, Cambridge, USA, Ma, 02138

Repository Status

  • Restricted

Socio-economic Objectives

Expanding knowledge in the biological sciences

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    University Of Tasmania

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