+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-24306 | |||||||||
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Title | Structure of the p97(R155H) dodecamer II | |||||||||
Map data | Structure of the p97(R155H) dodecamer II | |||||||||
Sample |
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Function / homology | Function and homology information positive regulation of Lys63-specific deubiquitinase activity / flavin adenine dinucleotide catabolic process / positive regulation of oxidative phosphorylation / VCP-NSFL1C complex / endosome to lysosome transport via multivesicular body sorting pathway / endoplasmic reticulum stress-induced pre-emptive quality control / cellular response to arsenite ion / Derlin-1 retrotranslocation complex / BAT3 complex binding / protein-DNA covalent cross-linking repair ...positive regulation of Lys63-specific deubiquitinase activity / flavin adenine dinucleotide catabolic process / positive regulation of oxidative phosphorylation / VCP-NSFL1C complex / endosome to lysosome transport via multivesicular body sorting pathway / endoplasmic reticulum stress-induced pre-emptive quality control / cellular response to arsenite ion / Derlin-1 retrotranslocation complex / BAT3 complex binding / protein-DNA covalent cross-linking repair / positive regulation of protein K63-linked deubiquitination / deubiquitinase activator activity / mitotic spindle disassembly / aggresome assembly / VCP-NPL4-UFD1 AAA ATPase complex / regulation of protein localization to chromatin / ubiquitin-modified protein reader activity / vesicle-fusing ATPase / NADH metabolic process / cellular response to misfolded protein / stress granule disassembly / positive regulation of mitochondrial membrane potential / negative regulation of protein localization to chromatin / K48-linked polyubiquitin modification-dependent protein binding / retrograde protein transport, ER to cytosol / regulation of aerobic respiration / positive regulation of ATP biosynthetic process / regulation of synapse organization / ATPase complex / ubiquitin-specific protease binding / ubiquitin-like protein ligase binding / MHC class I protein binding / autophagosome maturation / RHOH GTPase cycle / polyubiquitin modification-dependent protein binding / HSF1 activation / proteasomal protein catabolic process / endoplasmic reticulum to Golgi vesicle-mediated transport / translesion synthesis / Protein methylation / interstrand cross-link repair / ERAD pathway / ATP metabolic process / negative regulation of smoothened signaling pathway / endoplasmic reticulum unfolded protein response / Attachment and Entry / proteasome complex / viral genome replication / lipid droplet / Josephin domain DUBs / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / macroautophagy / Hh mutants are degraded by ERAD / Hedgehog ligand biogenesis / Defective CFTR causes cystic fibrosis / Translesion Synthesis by POLH / positive regulation of protein-containing complex assembly / establishment of protein localization / positive regulation of non-canonical NF-kappaB signal transduction / ABC-family proteins mediated transport / activation of cysteine-type endopeptidase activity involved in apoptotic process / ADP binding / autophagy / Aggrephagy / cytoplasmic stress granule / positive regulation of canonical Wnt signaling pathway / positive regulation of protein catabolic process / azurophil granule lumen / KEAP1-NFE2L2 pathway / double-strand break repair / Ovarian tumor domain proteases / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / E3 ubiquitin ligases ubiquitinate target proteins / Neddylation / site of double-strand break / cellular response to heat / protein phosphatase binding / ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / secretory granule lumen / regulation of apoptotic process / ficolin-1-rich granule lumen / Attachment and Entry / protein ubiquitination / protein domain specific binding / intracellular membrane-bounded organelle / DNA repair / DNA damage response / ubiquitin protein ligase binding / lipid binding / glutamatergic synapse / endoplasmic reticulum membrane / Neutrophil degranulation / perinuclear region of cytoplasm / endoplasmic reticulum / ATP hydrolysis activity / protein-containing complex / RNA binding / extracellular exosome / extracellular region Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.1 Å | |||||||||
Authors | Nandi P / Li S / Coulmbres RCA / Wang F / Williams DR / Poh Y-P / Chou T-F / Chiu P-L | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Int J Mol Sci / Year: 2021 Title: Structural and Functional Analysis of Disease-Linked p97 ATPase Mutant Complexes. Authors: Purbasha Nandi / Shan Li / Rod Carlo A Columbres / Feng Wang / Dewight R Williams / Yu-Ping Poh / Tsui-Fen Chou / Po-Lin Chiu / Abstract: IBMPFD/ALS is a genetic disorder caused by a single amino acid mutation on the p97 ATPase, promoting ATPase activity and cofactor dysregulation. The disease mechanism underlying p97 ATPase ...IBMPFD/ALS is a genetic disorder caused by a single amino acid mutation on the p97 ATPase, promoting ATPase activity and cofactor dysregulation. The disease mechanism underlying p97 ATPase malfunction remains unclear. To understand how the mutation alters the ATPase regulation, we assembled a full-length p97 with its p47 cofactor and first visualized their structures using single-particle cryo-EM. More than one-third of the population was the dodecameric form. Nucleotide presence dissociates the dodecamer into two hexamers for its highly elevated function. The N-domains of the p97 mutant all show up configurations in ADP- or ATPS-bound states. Our functional and structural analyses showed that the p47 binding is likely to impact the p97 ATPase activities via changing the conformations of arginine fingers. These functional and structural analyses underline the ATPase dysregulation with the miscommunication between the functional modules of the p97. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_24306.map.gz | 49.6 MB | EMDB map data format | |
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Header (meta data) | emd-24306-v30.xml emd-24306.xml | 9.5 KB 9.5 KB | Display Display | EMDB header |
Images | emd_24306.png | 106.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-24306 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24306 | HTTPS FTP |
-Validation report
Summary document | emd_24306_validation.pdf.gz | 352 KB | Display | EMDB validaton report |
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Full document | emd_24306_full_validation.pdf.gz | 351.5 KB | Display | |
Data in XML | emd_24306_validation.xml.gz | 6.2 KB | Display | |
Data in CIF | emd_24306_validation.cif.gz | 7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24306 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24306 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_24306.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Structure of the p97(R155H) dodecamer II | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.59 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : p97 R155H mutant
Entire | Name: p97 R155H mutant |
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Components |
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-Supramolecule #1: p97 R155H mutant
Supramolecule | Name: p97 R155H mutant / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli (E. coli) |
-Macromolecule #1: p97 R155H mutant in dodecameric form
Macromolecule | Name: p97 R155H mutant in dodecameric form / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MASGADSKGD DLSTAILKQK NRPNRLIVDE AINEDNSVVS LSQPKMDELQ LFRGDTVLLK GKKRREAVC IVLSDDTCSD EKIRMNRVVR NNLRVRLGDV ISIQPCPDVK YGKRIHVLPI D DTVEGITG NL FEVYLKP YFL EAYRPI RKGD IFLVH GGMRA VEFK ...String: MASGADSKGD DLSTAILKQK NRPNRLIVDE AINEDNSVVS LSQPKMDELQ LFRGDTVLLK GKKRREAVC IVLSDDTCSD EKIRMNRVVR NNLRVRLGDV ISIQPCPDVK YGKRIHVLPI D DTVEGITG NL FEVYLKP YFL EAYRPI RKGD IFLVH GGMRA VEFK VVETDPSPYC IVAPDT VIH CEGEPIKRED EEESLNEVGY DDIGGCRKQL AQIKEMVELP LRHPALFKAI GVKPPRG IL LYGPPGTGKT LIARAVANET GAFFFLINGP EIMSKLAGES ESNLRKAFEE AEKNAPAI I FIDELDAIAP KREKTHGEVE RRIVSQLLTL MDGLKQRAHV IVMAATNRPN SIDPALRRF GRFDREVDIG IPDATGRLEI LQIHTKNMKL ADDVDLEQVA NETHGHVGAD LAALCSEAAL QAIRKKMDL IDLEDETIDA EVMNSLAVTM DDFRWALSQS NPSALRETVV EVPQVTWEDI G GLEDVKRE LQELVQYPVE HPDKFLKFGM TPSKGVLFYG PPGCGKTLLA KAIANECQAN FI SIKGPEL LTMWFGESEA NVREIFDKAR QAAPCVLFFD ELDSIAKARG GNIGDGGGAA DRV INQILT EMDGMSTKKN VFIIGATNRP DIIDPAILRP GRLDQLIYIP LPDEKSRVAI LKAN LRKSP VAKDVDLEFL AKMTNGFSGA DLTEICQRAC KLAIRESIES EIRRERERQT NPSAM EVEE DDPVPEIRRD HFEEAMRFAR RSVSDNDIRK YEMFAQTLQQ SRGFGSFRFP SGNQGG AGP SQGSGGGTGG SVYTEDNDDD LYG |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 44.4 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 6.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 2219 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |