Architecture and Nucleotide-Dependent Conformational Changes of the Rvb1-Rvb2 AAA+ Complex Revealed by Cryoelectron Microscopy
| Autor: | Caroline A. Ewens, Liang Zhao, Nardin Nano, Walid A. Houry, Min Su, Daniel R. Southworth |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Plasma protein binding Molecular Dynamics Simulation 03 medical and health sciences 0302 clinical medicine Structural Biology ATP hydrolysis RUVBL2 Molecular Biology Ribonucleoprotein Binding Sites biology Nucleotides Cryoelectron Microscopy DNA Helicases Helicase AAA proteins Chromatin Molecular Docking Simulation 030104 developmental biology Dodecameric protein Biochemistry biology.protein Biophysics ATPases Associated with Diverse Cellular Activities Carrier Proteins 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Structure (London, England : 1993). 24(5) |
| ISSN: | 1878-4186 |
| Popis: | Rvb1 and Rvb2 are essential AAA+ proteins that interact together during the assembly and activity of diverse macromolecules including chromatin remodelers INO80 and SWR-C, and ribonucleoprotein complexes including telomerase and snoRNPs. ATP hydrolysis by Rvb1/2 is required for function; however, the mechanism that drives substrate remodeling is unknown. Here we determined the architecture of the yeast Rvb1/2 dodecamer using cryoelectron microscopy and identify that the substrate-binding insertion domain undergoes conformational changes in response to nucleotide state. 2D and 3D classification defines the dodecamer flexibility, revealing distinct arrangements and the hexamer-hexamer interaction interface. Reconstructions of the apo, ATP, and ADP states identify that Rvb1/2 undergoes substantial conformational changes that include a twist in the insertion-domain position and a corresponding rotation of the AAA+ ring. These results reveal how the ATP hydrolysis cycle of the AAA+ domains directs insertion-domain movements that could provide mechanical force during remodeling or helicase activities. |
| Databáze: | OpenAIRE |
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