The structural basis for the recognition of distorted dna structures by the drosophila high mobility group protein, hmg-d

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Project objective

Research objectives and content HMG-D is one the Drosophila counterparts of the mammalian HMG- 1 and 2 chromosomal proteins. These proteins are abundant but their functions are not well understood. HMG-D comprises a single HMG domain, which is the primary DNA binding motif, followed by a basic region and a C-terminal acidic tail. This acidic tail confers selectivity for the recognition of deformed DNA structures, such as bulged DNA and four-way junctions, and thereby modulates the binding of the protein to DNA. On the basis of footprinting studies it is proposed that HMG-D recognises a widened minor groove in such deformed structures and that a major determinant of this selective recognition is the loop connecting helices I and II. I plan to test this hypothesis by biochemical studies on the complex of HMG-D with bulged DNA and by designing and testing model peptides for bulged DNA recognition. The major goal of this project is to determine the solution structure of the complex of HMG-D with bulged DNA by NMR spectroscopy and in addition to determine whether the structure of the HMG domain is modulated by the acidic tail. Training content (objective, benefit and expected impact) Although the proposed project is in the same general area as my PhD work, in practice it will involve a substantial extension to my skills. The HMG system is significantly more demanding technically than AlcR (the subject of my PhD project), both because optimum conditions for the NMR experiments are much harder to establish, and because 13C labelling and triple resonance experiments will be required for me to complete the structure determination. It will be of great value for me to develop the necessary skills for this project in the context of a world-leading NMR group. Links with industry / industrial relevance (22) no link with industry

Original text from CORDIS.

Participants

• MRC Laboratory of Molecular Biology · CambridgeCoordinatorUnited Kingdom
• Not availableCity levelFrance

Links

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