Binding of transcription factor GabR to DNA requires recognition of DNA shape at a location distinct from its cognate binding site.

Autor:	Al-Zyoud WA; School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia., Hynson RM; The Victor Chang Cardiac Research Institute, 405 Liverpool St Darlinghurst, Darlinghurst, NSW 2010, Australia., Ganuelas LA; The Victor Chang Cardiac Research Institute, 405 Liverpool St Darlinghurst, Darlinghurst, NSW 2010, Australia., Coster AC; School of Mathematics and Statistics, University of New South Wales, Sydney, NSW 2052, Australia., Duff AP; Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW 2234, Australia., Baker MA; The Victor Chang Cardiac Research Institute, 405 Liverpool St Darlinghurst, Darlinghurst, NSW 2010, Australia., Stewart AG; The Victor Chang Cardiac Research Institute, 405 Liverpool St Darlinghurst, Darlinghurst, NSW 2010, Australia., Giannoulatou E; The Victor Chang Cardiac Research Institute, 405 Liverpool St Darlinghurst, Darlinghurst, NSW 2010, Australia., Ho JW; The Victor Chang Cardiac Research Institute, 405 Liverpool St Darlinghurst, Darlinghurst, NSW 2010, Australia., Gaus K; School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia EMBL Australia Node for Single Molecule Science, The University of New South Wales, Corner Botany and High Street, Kensington Campus 2052, NSW 2052, Australia., Liu D; Department of Chemistry and Biochemistry, Loyola University, Chicago, IL 60660, USA., Lee LK; School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia The Victor Chang Cardiac Research Institute, 405 Liverpool St Darlinghurst, Darlinghurst, NSW 2010, Australia EMBL Australia Node for Single Molecule Science, The University of New South Wales, Corner Botany and High Street, Kensington Campus 2052, NSW 2052, Australia lawrence.lee@unsw.edu.au., Böcking T; School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia EMBL Australia Node for Single Molecule Science, The University of New South Wales, Corner Botany and High Street, Kensington Campus 2052, NSW 2052, Australia till.boecking@unsw.edu.au.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2016 Feb 18; Vol. 44 (3), pp. 1411-20. Date of Electronic Publication: 2015 Dec 17.
DOI:	10.1093/nar/gkv1466
Abstrakt:	Mechanisms for transcription factor recognition of specific DNA base sequences are well characterized and recent studies demonstrate that the shape of these cognate binding sites is also important. Here, we uncover a new mechanism where the transcription factor GabR simultaneously recognizes two cognate binding sites and the shape of a 29 bp DNA sequence that bridges these sites. Small-angle X-ray scattering and multi-angle laser light scattering are consistent with a model where the DNA undergoes a conformational change to bend around GabR during binding. In silico predictions suggest that the bridging DNA sequence is likely to be bendable in one direction and kinetic analysis of mutant DNA sequences with biolayer interferometry, allowed the independent quantification of the relative contribution of DNA base and shape recognition in the GabR-DNA interaction. These indicate that the two cognate binding sites as well as the bendability of the DNA sequence in between these sites are required to form a stable complex. The mechanism of GabR-DNA interaction provides an example where the correct shape of DNA, at a clearly distinct location from the cognate binding site, is required for transcription factor binding and has implications for bioinformatics searches for novel binding sites. (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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