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Fine-tuning of intrinsic N-Oct-3 POU domain allostery by regulatory DNA targetsстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 3 декабря 2017 г.
- Авторы: Alazard Robert, Mourey Lionel, Ebel Christine, Konarev Peter V., Petoukhov Maxim V., Svergun Dmitri I., Erard Monique
- Журнал: Nucleic Acids Research
- Том: 35
- Номер: 13
- Год издания: 2007
- Издательство: Oxford University Press
- Местоположение издательства: United Kingdom
- Первая страница: 4420
- Последняя страница: 4432
- DOI: 10.1093/nar/gkm453
- Аннотация: The ‘POU’ (acronym of Pit-1, Oct-1, Unc-86) family of transcription factors share a common DNA-binding domain of approximately 160 residues, comprising so-called ‘POUs’ and ‘POUh’ sub-domains connected by a flexible linker. The importance of POU proteins as developmental regulators and tumor-promoting agents is due to linker flexibility, which allows them to adapt to a considerable variety of DNA targets. However, because of this flexibility, it has not been possible to determine the Oct-1/Pit-1 linker structure in crystallographic POU/DNA complexes. We have previously shown that the neuronal POU protein N-Oct-3 linker contains a structured region. Here, we have used a combination of hydrodynamic methods, DNA footprinting experiments, molecular modeling and small angle X-ray scattering to (i) structurally interpret the N-Oct-3-binding site within the H LA DR alpha gene promoter and deduce from this a novel POU domain allosteric conformation and (ii) analyze the molecular mechanisms involved in conformational transitions. We conclude that there might exist a continuum running from free to ‘pre-bound’ N-Oct-3 POU conformations and that regulatory DNA regions likely select pre-existing conformers, in addition to molding the appropriate DBD structure. Finally, we suggest that a specific pair of glycine residues in the linker might act as a major conformational switch.
- Добавил в систему: Петухов Максим Владимирович