25-30 August 2019
Henry Ford Building
Europe/Berlin timezone

Structural description of the target search process by a disordered transcription factor

26 Aug 2019, 16:50
Lecture Hall C (Henry Ford Building)

Lecture Hall C

Henry Ford Building

Talk Biological applications Biomolecules


Mr Conor Kelly (University of Oxford)


Specific transcription factors must search for their target sites amongst a vast excess of non-specific DNA. They find their sites quickly using a combination of sliding, jumping, hopping and intersegmental transfer. DNA binding domains (DBDs) are usually thought of as structured, however this is not always the case. There are also 3 very large classes of transcription factors whose DBD are disordered in the absence of DNA – bZIPs, bHLH and AT hooks. I have been examining a prominent model protein, cyclic-AMP response element binding (CREB) protein, a member of the bZIP family, to determine what role protein disorder might play in the target search process. CREB binds to its target as a homodimer. We present structural data from NMR for both monomeric and dimeric CREB that describes its secondary structure propensity and dynamics when free in solution, sliding along the DNA and bound to its target site. We demonstrate that whilst searching for its target site the protein remains highly dynamic with limited helical content, and that the protein forms a dimer before binding to its target site. To our knowledge our results constitute the most complete structural description of the search process by a disordered transcription factor to date.

Primary authors

Mr Conor Kelly (University of Oxford) Prof. Christina Redfield (University of Oxford) Dr Sarah Shammas (University of Oxford)

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