title: The coiled-coil of the human Rad50 DNA repair protein contains specific segments of increased flexibility.
abstract: Protein structural features are usually determined by defining regularities in a large population of homogeneous molecules. However, irregular features such as structural variation and flexibility are likely to be missed, despite their vital role for their biological function. In this paper, we report the observation of striking irregularities in the flexibility of the coiled-coil region of the human Rad50 DNA repair protein. Existing methods to quantitatively analyze flexibility are applicable to homogeneous polymers only. Because protein coiled-coils cannot be assumed to be homogeneous, we develop a method to quantify the local flexibility from high-resolution atomic force microscopy images. Indeed, in Rad50 coiled-coils, two positions of increased flexibility are observed. We discuss how this dynamic structural feature is integral to Rad50 function.
authors.affiliation: Department of Nanoscience and Delft Institute of Microelectronics and Submicrontechnology, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, The Netherlands. noort@mb.tn.tudelft.nl
authors.forename: John
authors.initials: J
authors.lastname: van Noort
authors.forename: Thijn
authors.initials: T
authors.lastname: van Der Heijden
authors.forename: Martijn
authors.initials: M
authors.lastname: de Jager
authors.forename: Claire
authors.initials: C
authors.lastname: Wyman
authors.forename: Roland
authors.initials: R
authors.lastname: Kanaar
authors.forename: Cees
authors.initials: C
authors.lastname: Dekker
mesh_terms: D055592:Biophysical Phenomena; D001703:Biophysics; D004247:DNA / Q000032:analysis; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D015233:Models, Statistical; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C086930:RAD50 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA