An intrinsically disordered motif regulates the interaction between the p47 adaptor and the p97 AAA+ ATPase
| Autor: | Eric Wang, Zev A Ripstein, John L. Rubinstein, Alexander E. Conicella, Ai Nguyen, Lewis E. Kay, Peter Schuck, Rui Huang, Thomas Löhr, Michele Vendruscolo |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
inorganic chemicals
Models Molecular congenital hereditary and neonatal diseases and abnormalities Cryo-electron microscopy Protein Conformation Amino Acid Motifs 03 medical and health sciences chemistry.chemical_compound Adenosine Triphosphate hemic and lymphatic diseases Humans Nucleotide Short linear motif Lipid bilayer 030304 developmental biology Adaptor Proteins Signal Transducing chemistry.chemical_classification Adenosine Triphosphatases 0303 health sciences Multidisciplinary Chemistry 030302 biochemistry & molecular biology Nuclear Proteins hemic and immune systems Biological Sciences AAA proteins Adenosine Diphosphate Intrinsically Disordered Proteins Adenosine diphosphate Proteostasis Biophysics Adenosine triphosphate circulatory and respiratory physiology Protein Binding |
| Zdroj: | Proc Natl Acad Sci U S A |
| Popis: | VCP/p97, an enzyme critical to proteostasis, is regulated through interactions with protein adaptors targeting it to specific cellular tasks. One such adaptor, p47, forms a complex with p97 to direct lipid membrane remodeling. Here, we use NMR and other biophysical methods to study the structural dynamics of p47 and p47-p97 complexes. Disordered regions in p47 are shown to be critical in directing intra-p47 and p47-p97 interactions via a pair of previously unidentified linear motifs. One of these, an SHP domain, regulates p47 binding to p97 in a manner that depends on the nucleotide state of p97. NMR and electron cryomicroscopy data have been used as restraints in molecular dynamics trajectories to develop structural ensembles for p47-p97 complexes in adenosine diphosphate (ADP)- and adenosine triphosphate (ATP)-bound conformations, highlighting differences in interactions in the two states. Our study establishes the importance of intrinsically disordered regions in p47 for the formation of functional p47-p97 complexes. |
| Databáze: | OpenAIRE |
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