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Yorodumi- PDB-7q08: Structure of Candida albicans 80S ribosome in complex with cycloh... -
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-Basic information
Entry | Database: PDB / ID: 7q08 | ||||||||||||||||||
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Title | Structure of Candida albicans 80S ribosome in complex with cycloheximide | ||||||||||||||||||
Components |
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Keywords | RIBOSOME / Candida albicans / cycloheximide / drug design | ||||||||||||||||||
Function / homology | Function and homology information filamentous growth of a population of unicellular organisms in response to neutral pH / cellular response to neutral pH / negative regulation of cell integrity MAPK cascade / positive regulation of conjugation with cellular fusion / filamentous growth of a population of unicellular organisms in response to biotic stimulus / filamentous growth of a population of unicellular organisms in response to starvation / yeast-form cell wall / GCN2-mediated signaling / regulation of cytoplasmic translation / fungal biofilm matrix ...filamentous growth of a population of unicellular organisms in response to neutral pH / cellular response to neutral pH / negative regulation of cell integrity MAPK cascade / positive regulation of conjugation with cellular fusion / filamentous growth of a population of unicellular organisms in response to biotic stimulus / filamentous growth of a population of unicellular organisms in response to starvation / yeast-form cell wall / GCN2-mediated signaling / regulation of cytoplasmic translation / fungal biofilm matrix / hyphal cell wall / invasive growth in response to glucose limitation / triplex DNA binding / negative regulation of p38MAPK cascade / ribosome hibernation / translation elongation factor binding / regulation of translational initiation in response to stress / filamentous growth / negative regulation of glucose mediated signaling pathway / negative regulation of translational frameshifting / positive regulation of translational fidelity / ribosome-associated ubiquitin-dependent protein catabolic process / GDP-dissociation inhibitor activity / pre-mRNA 5'-splice site binding / preribosome, small subunit precursor / telomeric DNA binding / mRNA destabilization / negative regulation of mRNA splicing, via spliceosome / translational elongation / G-protein alpha-subunit binding / TOR signaling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / protein-RNA complex assembly / ribosomal subunit export from nucleus / ribosomal small subunit export from nucleus / positive regulation of autophagy / translation regulator activity / translation repressor activity / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / DNA-(apurinic or apyrimidinic site) endonuclease activity / maturation of LSU-rRNA / telomere maintenance / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / cellular response to starvation / rescue of stalled ribosome / ribosomal large subunit biogenesis / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of SSU-rRNA / small-subunit processome / protein kinase C binding / maintenance of translational fidelity / modification-dependent protein catabolic process / protein tag activity / rRNA processing / ribosomal small subunit biogenesis / small ribosomal subunit rRNA binding / extracellular vesicle / ribosome biogenesis / ribosome binding / ribosomal small subunit assembly / large ribosomal subunit rRNA binding / 5S rRNA binding / small ribosomal subunit / cytosolic small ribosomal subunit / ribosomal large subunit assembly / cytoplasmic translation / cytosolic large ribosomal subunit / negative regulation of translation / cell adhesion / rRNA binding / ribosome / protein ubiquitination / structural constituent of ribosome / translation / ribonucleoprotein complex / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / mRNA binding / ubiquitin protein ligase binding / negative regulation of apoptotic process / nucleolus / cell surface / RNA binding / zinc ion binding / extracellular region / membrane / nucleus / metal ion binding / cytosol / cytoplasm Similarity search - Function | ||||||||||||||||||
Biological species | Candida albicans SC5314 (yeast) | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.56 Å | ||||||||||||||||||
Authors | Zgadzay, Y. / Kolosova, O. / Stetsenko, A. / Jenner, L. / Guskov, A. / Yusupova, G. / Yusupov, M. | ||||||||||||||||||
Funding support | France, 5items
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Citation | Journal: Sci Adv / Year: 2022 Title: E-site drug specificity of the human pathogen ribosome. Authors: Yury Zgadzay / Olga Kolosova / Artem Stetsenko / Cheng Wu / David Bruchlen / Konstantin Usachev / Shamil Validov / Lasse Jenner / Andrey Rogachev / Gulnara Yusupova / Matthew S Sachs / ...Authors: Yury Zgadzay / Olga Kolosova / Artem Stetsenko / Cheng Wu / David Bruchlen / Konstantin Usachev / Shamil Validov / Lasse Jenner / Andrey Rogachev / Gulnara Yusupova / Matthew S Sachs / Albert Guskov / Marat Yusupov / Abstract: is a widespread commensal fungus with substantial pathogenic potential and steadily increasing resistance to current antifungal drugs. It is known to be resistant to cycloheximide (CHX) that binds ... is a widespread commensal fungus with substantial pathogenic potential and steadily increasing resistance to current antifungal drugs. It is known to be resistant to cycloheximide (CHX) that binds to the E-transfer RNA binding site of the ribosome. Because of lack of structural information, it is neither possible to understand the nature of the resistance nor to develop novel inhibitors. To overcome this issue, we determined the structure of the vacant 80 ribosome at 2.3 angstroms and its complexes with bound inhibitors at resolutions better than 2.9 angstroms using cryo-electron microscopy. Our structures reveal how a change in a conserved amino acid in ribosomal protein eL42 explains CHX resistance in and forms a basis for further antifungal drug development. | ||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7q08.cif.gz | 4.3 MB | Display | PDBx/mmCIF format |
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PDB format | pdb7q08.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 7q08.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7q08_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 7q08_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 7q08_validation.xml.gz | 266.2 KB | Display | |
Data in CIF | 7q08_validation.cif.gz | 451.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/q0/7q08 ftp://data.pdbj.org/pub/pdb/validation_reports/q0/7q08 | HTTPS FTP |
-Related structure data
Related structure data | 13741MC 7pzyC 7q0fC 7q0pC 7q0rC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-RNA chain , 4 types, 4 molecules 134A
#1: RNA chain | Mass: 1085306.250 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: GenBank: 1078736431 |
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#2: RNA chain | Mass: 38943.129 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: GenBank: 1111963231 |
#3: RNA chain | Mass: 50683.906 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) |
#46: RNA chain | Mass: 575838.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / References: GenBank: 1078736431 |
+Ribosomal 60S subunit protein ... , 28 types, 28 molecules jklmoqrsuwxy256789ABADAEAFAGAHAIALAPAQ
-60S ribosomal protein ... , 9 types, 9 molecules npt0AAACAJAMAO
#8: Protein | Mass: 19798.002 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PCX8 |
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#10: Protein | Mass: 28549.424 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: Q5ANA1 |
#14: Protein | Mass: 23105.771 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: O59931 |
#21: Protein | Mass: 20376.859 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PLC9 |
#28: Protein | Mass: 15551.407 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PFG4 |
#30: Protein | Mass: 7135.336 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PF57 |
#37: Protein | Mass: 11096.161 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PH21 |
#40: Protein | Mass: 6347.549 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PDT4 |
#42: Protein/peptide | Mass: 3396.280 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) |
-Ribosomal protein ... , 3 types, 3 molecules vzAK
#16: Protein | Mass: 24389.256 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: Q5A6R1 |
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#20: Protein | Mass: 21942.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PK40 |
#38: Protein | Mass: 10102.830 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PF45 |
-Protein , 4 types, 4 molecules ANigh
#41: Protein | Mass: 6078.412 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PL68 |
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#45: Protein | Mass: 29126.141 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PK71 |
#78: Protein | Mass: 22615.525 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: Q5A109 |
#79: Protein | Mass: 34593.934 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: P83774 |
-40S ribosomal protein ... , 14 types, 14 molecules BCFHIJNWXZabcf
#47: Protein | Mass: 28759.307 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: O42817 |
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#48: Protein | Mass: 29041.859 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: P40910 |
#51: Protein | Mass: 29435.354 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PCI6 |
#53: Protein | Mass: 27146.469 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PL99 |
#54: Protein | Mass: 21285.818 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: Q5AJ93 |
#55: Protein | Mass: 22801.979 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: Q59T44 |
#59: Protein | Mass: 15715.855 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: Q5ADQ6 |
#68: Protein | Mass: 9652.814 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PCG7 |
#69: Protein | Mass: 14807.189 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: Q96W54 |
#71: Protein | Mass: 15546.922 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: Q5A7K0 |
#72: Protein | Mass: 11633.762 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PNQ6 |
#73: Protein | Mass: 13606.099 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: Q5ALV6 |
#74: Protein | Mass: 8982.504 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PTI7 |
#77: Protein | Mass: 7127.437 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PSK2 |
-Ribosomal 40S subunit protein ... , 17 types, 17 molecules DEGKLMOPQRSTUVYde
#49: Protein | Mass: 26917.314 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: Q5A900 |
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#50: Protein | Mass: 27313.570 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PSV5 |
#52: Protein | Mass: 25319.922 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: Q5AG43 |
#56: Protein | Mass: 21765.146 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PGY8 |
#57: Protein | Mass: 13836.824 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PI15 |
#58: Protein | Mass: 17638.648 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PN83 |
#60: Protein | Mass: 16976.787 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PPE0 |
#61: Protein | Mass: 14052.112 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PDT3 |
#62: Protein | Mass: 15967.796 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PK22 |
#63: Protein | Mass: 15769.456 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PCW6 |
#64: Protein | Mass: 15770.298 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PEY9 |
#65: Protein | Mass: 17023.785 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PQQ5 |
#66: Protein | Mass: 16097.218 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PK61 |
#67: Protein | Mass: 13366.540 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: Q5A389 |
#70: Protein | Mass: 16000.784 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PDU3 |
#75: Protein | Mass: 7536.808 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PQN0 |
#76: Protein | Mass: 6615.582 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Candida albicans SC5314 (yeast) / Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PTR4 |
-Non-polymers , 3 types, 10 molecules
#80: Chemical | ChemComp-SPD / |
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#81: Chemical | ChemComp-3HE / |
#82: Chemical | ChemComp-ZN / |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Candida albicans 80S ribosome / Type: RIBOSOME / Entity ID: #1-#79 / Source: NATURAL |
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Molecular weight | Value: 3.3 MDa / Experimental value: NO |
Source (natural) | Organism: Candida albicans SC5314 (yeast) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE-PROPANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: OTHER / Nominal defocus max: 2400 nm / Nominal defocus min: 900 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 2.56 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 180636 / Symmetry type: POINT |