Structural Architecture of the Nucleosome Remodeler ISWI Determined from Cross-Linking, Mass Spectrometry, SAXS, and Modeling
| Autor: | Johanna Ludwigsen, Jan Lipfert, Nadine Harrer, Martin Zacharias, Linda K. Bruetzel, Felix Mueller-Planitz, Ignasi Forné, Christina E. M. Schindler, Axel Imhof |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular ATPase Mass spectrometry Chromatin remodeling Mass Spectrometry 03 medical and health sciences chemistry.chemical_compound X-Ray Diffraction Structural Biology Scattering Small Angle Nucleosome Animals Drosophila Proteins Molecular Biology Structural approach Adenosine Triphosphatases biology Small-angle X-ray scattering Chromatin Assembly and Disassembly Chromatin Nucleosomes 030104 developmental biology Drosophila melanogaster chemistry biology.protein Biophysics DNA Protein Binding Transcription Factors |
| Zdroj: | Structure (London, England : 1993). 26(2) |
| ISSN: | 1878-4186 |
| Popis: | Chromatin remodeling factors assume critical roles by regulating access to nucleosomal DNA. To determine the architecture of the Drosophila ISWI remodeling enzyme, we developed an integrative structural approach that combines protein cross-linking, mass spectrometry, small-angle X-ray scattering, and computational modeling. The resulting structural model shows the ATPase module in a resting state with both ATPase lobes twisted against each other, providing support for a conformation that was recently trapped by crystallography. The autoinhibiting NegC region does not protrude from the ATPase module as suggested previously. The regulatory NTR domain is located near both ATPase lobes. The full-length enzyme is flexible and can adopt a compact structure in solution with the C-terminal HSS domain packing against the ATPase module. Our data imply a series of conformational changes upon activation of the enzyme and illustrate how the NTR, NegC, and HSS domains contribute to regulation of the ATPase module. |
| Databáze: | OpenAIRE |
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