التفاصيل البيبلوغرافية
| العنوان: |
Crystal structure of the catalytic D2 domain of the AAA+ ATPase p97 reveals a putative helical split-washer-type mechanism for substrate unfolding |
| المؤلفون: |
Xiaodong Zhang, Linda Makhlouf, Frank von Delft, Paul S. Freemont, Rhodri M. L. Morgan, Alice Douangamath, Lasse Stach |
| المساهمون: |
Cancer Research UK |
| المصدر: |
Febs Letters |
| سنة النشر: |
2019 |
| مصطلحات موضوعية: |
Models, Molecular, Protein Conformation, alpha-Helical, p97, VALOSIN-CONTAINING PROTEIN, ATPase, Protein Data Bank (RCSB PDB), Druggability, CRYO-EM, 0601 Biochemistry and Cell Biology, Crystallography, X-Ray, Biochemistry, DISEASE, ATP hydrolysis, Valosin Containing Protein, Structural Biology, Catalytic Domain, BINDING, PROTEASOME, chemistry.chemical_classification, 0303 health sciences, biology, Chemistry, 030302 biochemistry & molecular biology, AAA plus ATPase, IBMPFD, CANCER, AAA proteins, AAA+ ATPase, Life Sciences & Biomedicine, Protein Binding, Biochemistry & Molecular Biology, Valosin-containing protein, Biophysics, information science, 03 medical and health sciences, 0603 Evolutionary Biology, Protein Domains, Genetics, Research Letter, Humans, natural sciences, D2 domain, Molecular Biology, P97/VCP, 030304 developmental biology, Science & Technology, COMPLEX, 0304 Medicinal and Biomolecular Chemistry, Cell Biology, Research Letters, Enzyme, Proteasome, LINK, Mutation, biology.protein, SYSTEM |
| الوصف: |
Several pathologies have been associated with the AAA+ ATPase p97, an enzyme essential to protein homeostasis. Heterozygous polymorphisms in p97 have been shown to cause neurological disease, while elevated proteotoxic stress in tumours has made p97 an attractive cancer chemotherapy target. The cellular processes reliant on p97 are well described. High‐resolution structural models of its catalytic D2 domain, however, have proved elusive, as has the mechanism by which p97 converts the energy from ATP hydrolysis into mechanical force to unfold protein substrates. Here, we describe the high‐resolution structure of the p97 D2 ATPase domain. This crystal system constitutes a valuable tool for p97 inhibitor development and identifies a potentially druggable pocket in the D2 domain. In addition, its P61 symmetry suggests a mechanism for substrate unfolding by p97. Database The atomic coordinates and structure factors have been deposited in the PDB database under the accession numbers http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6G2V, http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6G2W, http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6G2X, http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6G2Y, http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6G2Z and http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6G30. |
| تدمد: |
1873-3468 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3049cfe4230d28b72fadb13c277ef71f
https://pubmed.ncbi.nlm.nih.gov/31701538 |
| حقوق: |
OPEN |
| رقم الأكسشن: |
edsair.doi.dedup.....3049cfe4230d28b72fadb13c277ef71f |
| قاعدة البيانات: |
OpenAIRE |
