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Protein flexibility directs DNA recognition by the papillomavirus E2 proteins

Brown, Craig A.; Campos-León, Karen; Strickland, Maddy; Williams, Christopher; Fairweather, Victoria; Brady, R. Leo; Crump, Matthew P.; Gaston, Kevin


Craig A. Brown

Karen Campos-León

Maddy Strickland

Christopher Williams

Victoria Fairweather

R. Leo Brady

Matthew P. Crump

Kevin Gaston


Although DNA flexibility is known to play an important role in DNA–protein interactions, the importance of protein flexibility is less well understood. Here, we show that protein dynamics are important in DNA recognition using the well-characterized human papillomavirus (HPV) type 6 E2 protein as a model system. We have compared the DNA binding properties of the HPV 6 E2 DNA binding domain (DBD) and a mutant lacking two C-terminal leucine residues that form part of the hydrophobic core of the protein. Deletion of these residues results in increased specific and non-specific DNA binding and an overall decrease in DNA binding specificity. Using 15N NMR relaxation and hydrogen/deuterium exchange, we demonstrate that the mutation results in increased flexibility within the hydrophobic core and loop regions that orient the DNA binding helices. Stopped-flow kinetic studies indicate that increased flexibility alters DNA binding by increasing initial interactions with DNA but has little or no effect on the structural rearrangements that follow this step. Taken together these data demonstrate that subtle changes in protein dynamics have a major influence on protein–DNA interactions.

Journal Article Type Article
Publication Date Apr 1, 2011
Journal Nucleic Acids Research
Print ISSN 0305-1048
Publisher Oxford University Press (OUP)
Peer Reviewed Peer Reviewed
Volume 39
Issue 7
Pages 2969--2980
APA6 Citation Brown, C. A., Campos-León, K., Strickland, M., Williams, C., Fairweather, V., Brady, R. L., …Gaston, K. (2011). Protein flexibility directs DNA recognition by the papillomavirus E2 proteins. Nucleic Acids Research, 39(7), 2969--2980. doi:10.1093/nar/gkq1217
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