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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, JPThe 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
StructureVolume
11Issue
7Pagination
803-813ISSN
0969-2126Department/School
Menzies Institute for Medical ResearchPublisher
Cell PressPlace of publication
1100 Massachusetts Ave, Cambridge, USA, Ma, 02138Repository Status
- Restricted