A combinatorial method to enable detailed investigation of protein–protein interactions

Maclagan, Kate, Tommasi, Rita, Laurine, Emmanuelle, Prodromou, Chrisostomos, Driscoll, Paul C, Pearl, Laurence H, Reich, Stefanie and Savva, Renos (2011) A combinatorial method to enable detailed investigation of protein–protein interactions. Future Medicinal Chemistry, 3 (3). pp. 271-282. ISSN 1756-8919

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Abstract

BACKGROUND: Successful structural investigations of protein-protein interactions can be facilitated by studying only the core interacting regions of the constituent proteins. However, attempting the discovery of stable core complexes using informed trial-and-error approaches can prove time and resource intensive. METHODS: We describe a valuable extension of combinatorial domain hunting (CDH), a technology for the timely elucidation of soluble protein truncations. The new method, CDH(2), enables empirical discovery of stable protein-protein core complexes. CDH(2) is demonstrated ab initio using a previously well-characterized Hsp90/Cdc37 complex. RESULTS: Without using a priori information, we demonstrate the isolation of stable protein-protein complexes, suitable for further analyses. DISCUSSION: This resource-efficient process can provide protein complexes for screening of compounds designed to modulate protein-protein interactions, thus facilitating novel drug discovery.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Chrisostomos Prodromou
Date Deposited: 06 Feb 2012 20:28
Last Modified: 02 Apr 2012 09:39
URI: http://sro.sussex.ac.uk/id/eprint/26025
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