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- PDB-6bi8: X-ray structure of MERS coronavirus papain-like protease in compl... -

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Basic information

Entry
Database: PDB / ID: 6bi8
TitleX-ray structure of MERS coronavirus papain-like protease in complex with human ISG15
Components
  • ORF1a
  • Ubiquitin-like protein ISG15
KeywordsHYDROLASE/SUBSTRATE / Complex / signaling protein / deISGylase / HYDROLASE / HYDROLASE-SUBSTRATE complex
Function / homology
Function and homology information


ISG15-protein conjugation / positive regulation of protein oligomerization / mRNA capping enzyme complex / regulation of type II interferon production / NS1 Mediated Effects on Host Pathways / protein localization to mitochondrion / response to type I interferon / Modulation of host responses by IFN-stimulated genes / negative regulation of type I interferon-mediated signaling pathway / negative regulation of viral genome replication ...ISG15-protein conjugation / positive regulation of protein oligomerization / mRNA capping enzyme complex / regulation of type II interferon production / NS1 Mediated Effects on Host Pathways / protein localization to mitochondrion / response to type I interferon / Modulation of host responses by IFN-stimulated genes / negative regulation of type I interferon-mediated signaling pathway / negative regulation of viral genome replication / RSV-host interactions / positive regulation of interleukin-10 production / host cell membrane / 7-methylguanosine mRNA capping / positive regulation of bone mineralization / negative regulation of protein ubiquitination / positive regulation of interferon-beta production / viral genome replication / positive regulation of erythrocyte differentiation / methyltransferase activity / integrin-mediated signaling pathway / Negative regulators of DDX58/IFIH1 signaling / Termination of translesion DNA synthesis / PKR-mediated signaling / DDX58/IFIH1-mediated induction of interferon-alpha/beta / response to virus / modification-dependent protein catabolic process / ISG15 antiviral mechanism / positive regulation of type II interferon production / protein tag activity / Interferon alpha/beta signaling / integrin binding / host cell endoplasmic reticulum-Golgi intermediate compartment / 3'-5'-RNA exonuclease activity / 5'-3' DNA helicase activity / symbiont-mediated degradation of host mRNA / symbiont-mediated suppression of host ISG15-protein conjugation / G-quadruplex RNA binding / omega peptidase activity / endonuclease activity / methylation / symbiont-mediated perturbation of host ubiquitin-like protein modification / symbiont-mediated suppression of host NF-kappaB cascade / defense response to virus / methyltransferase cap1 activity / cysteine-type deubiquitinase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / forked DNA-dependent helicase activity / single-stranded 3'-5' DNA helicase activity / four-way junction helicase activity / double-stranded DNA helicase activity / single-stranded RNA binding / RNA helicase activity / regulation of autophagy / host cell perinuclear region of cytoplasm / viral protein processing / lyase activity / defense response to bacterium / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / symbiont-mediated suppression of host gene expression / viral translational frameshifting / symbiont-mediated activation of host autophagy / innate immune response / cysteine-type endopeptidase activity / viral RNA genome replication / RNA-directed RNA polymerase activity / DNA-templated transcription / ubiquitin protein ligase binding / SARS-CoV-2 activates/modulates innate and adaptive immune responses / proteolysis / extracellular region / zinc ion binding / nucleoplasm / ATP binding / identical protein binding / nucleus / membrane / cytosol / cytoplasm
Similarity search - Function
Papain-like viral protease, thumb domain / Jelly Rolls - #1680 / RNA-dependent RNA polymerase, Middle East respiratory syndrome-related coronavirus / Non-structural protein 2, MERS-CoV-like / : / NSP3, SUD-C domain, MERS-CoV-like / AAA domain / Helicase, Ruva Protein; domain 3 / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 1 / Ubiquitin domain ...Papain-like viral protease, thumb domain / Jelly Rolls - #1680 / RNA-dependent RNA polymerase, Middle East respiratory syndrome-related coronavirus / Non-structural protein 2, MERS-CoV-like / : / NSP3, SUD-C domain, MERS-CoV-like / AAA domain / Helicase, Ruva Protein; domain 3 / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 1 / Ubiquitin domain / Ubiquitin-like (UB roll) / Ubiquitin family / Nonstructural protein 14, betacoronavirus / Nonstructural protein 15, middle domain, alpha/betacoronavirus / Nonstructural protein 15, N-terminal domain, alpha/beta-coronavirus / NSP14, guanine-N7-methyltransferase domain, coronavirus / Coronavirus (CoV) guanine-N7-methyltransferase (N7-MTase) domain profile. / Coronavirus (CoV) Nsp15 N-terminal oligomerization domain profile. / NSP12 RNA-dependent RNA polymerase, coronavirus / : / Coronavirus Nsp12 RNA-dependent RNA polymerase (RdRp) domain profile. / Coronavirus Nsp12 Interface domain profile. / : / : / Coronavirus Nonstructural protein 13, 1B domain / Coronavirus Non-structural protein 13, zinc-binding domain / Coronavirus Nonstructural protein 13, stalk domain / Nidovirus 2-O-methyltransferase / Nidovirus 2'-O-methyltransferase (2'-O-MTase) domain profile. / Non-structural protein NSP15, N-terminal domain superfamily, coronavirus / Non-structural protein NSP15, middle domain superfamily / Coronavirus replicase NSP15, N-terminal oligomerization / Nonstructural protein 15, middle domain, coronavirus / Nonstructural protein 13, 1B domain, coronavirus / Coronavirus replicase NSP15, middle domain / Coronavirus replicase NSP15, N-terminal oligomerisation / Nidovirus 3'-5' exoribonuclease domain / Nidovirus 3'-5' exoribonuclease (ExoN) domain profile. / Non-structural protein NSP16, coronavirus-like / Non-structural protein 14, coronavirus / RNA polymerase, N-terminal, coronavirus / Coronavirus 2'-O-methyltransferase / Coronavirus proofreading exoribonuclease / Coronavirus RNA-dependent RNA polymerase, N-terminal / Nonstructural protein 13, zinc-binding domain, coronavirus-like / Coronaviridae zinc-binding (CV ZBD) domain profile. / Arterivirus Nsp11 N-terminal/Coronavirus NSP15 middle domain / Arterivirus Nsp11 N-terminal/coronavirus NSP15 middle (AV-Nsp11N/CoV-Nsp15M) domain profile. / Nidoviral uridylate-specific endoribonuclease (NendoU) domain profile. / Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain / Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain profile. / Endoribonuclease EndoU-like / NendoU domain, nidovirus / Coronavirus replicase NSP15, uridylate-specific endoribonuclease / Ubiquitin homologues / : / Ubiquitin domain profile. / Ubiquitin-like domain / DNA2/NAM7 helicase-like, C-terminal / AAA domain / (+) RNA virus helicase core domain / (+)RNA virus helicase core domain profile. / Betacoronavirus Nsp3c-M domain profile. / NSP1, globular domain, betacoronavirus / Non-structural protein NSP3, SUD-M domain, betacoronavirus / Non-structural protein NSP3, SUD-M domain superfamily, betacoronavirus / Betacoronavirus replicase NSP1 / Betacoronavirus single-stranded poly(A) binding domain / NSP1, C-terminal domain, betacoronavirus / : / Betacoronavirus (BetaCoV) Nsp1 C-terminal domain profile. / Betacoronavirus Nsp3e group 2-specific marker (G2M) domain profile. / Betacoronavirus Nsp3c-C domain profile. / Betacoronavirus Nsp3e nucleic acid-binding (NAB) domain profile. / DPUP/SUD, C-terminal, betacoronavirus / Non-structural protein NSP3, nucleic acid-binding domain, betacoronavirus / Non-structural protein NSP3A domain-like superfamily / Non-structural protein NSP3, nucleic acid-binding domain superfamily, betacoronavirus / Non-structural protein 6, betacoronavirus / Betacoronavirus nucleic acid-binding (NAB) / Papain-like viral protease, palm and finger domains, coronavirus / Papain-like protease, N-terminal domain superfamily, coronavirus / Coronavirus replicase NSP2, N-terminal / : / Coronavirus replicase NSP2, C-terminal / Coronavirus (CoV) Nsp2 middle domain profile. / NSP1, globular domain, alpha/betacoronavirus / Coronavirus (CoV) Nsp1 globular domain profile. / Coronavirus (CoV) Nsp2 N-terminal domain profile. / Coronavirus (CoV) Nsp2 C-terminal domain profile. / Nonstructural protein 2, N-terminal domain, coronavirus / Non-structural protein 2, C-terminal domain, coronavirus / NSP3, second ubiquitin-like (Ubl) domain, coronavirus / Coronavirus Nsp3a Ubl domain profile. / Coronavirus Nsp3d Ubl domain profile. / NSP3, first ubiquitin-like (Ubl) domain, coronavirus / Peptidase family C16 domain profile. / : / : / Coronavirus replicase NSP7
Similarity search - Domain/homology
prop-2-en-1-amine / CITRIC ACID / TRIETHYLENE GLYCOL / ORF1ab polyprotein / ORF1a / Ubiquitin-like protein ISG15
Similarity search - Component
Biological speciesHuman betacoronavirus 2c EMC/2012
Homo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.291 Å
AuthorsClasman, J.C. / Mesecar, A.D.
Funding support United States, 3items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI085089 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)CA023168 United States
MEDC085P1000817 United States
CitationJournal: Antiviral Res. / Year: 2020
Title: Decoupling deISGylating and deubiquitinating activities of the MERS virus papain-like protease.
Authors: Clasman, J.R. / Everett, R.K. / Srinivasan, K. / Mesecar, A.D.
History
DepositionNov 1, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 7, 2018Provider: repository / Type: Initial release
Revision 1.1Feb 20, 2019Group: Author supporting evidence / Data collection / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.2Nov 27, 2019Group: Data collection / Refinement description / Category: refine / reflns / reflns_shell
Item: _refine.details / _refine.ls_d_res_high ..._refine.details / _refine.ls_d_res_high / _refine.ls_number_reflns_R_free / _refine.pdbx_stereochemistry_target_values / _reflns.d_resolution_high / _reflns_shell.d_res_high
Revision 1.3Dec 4, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.4May 20, 2020Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.5Oct 4, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / refine_hist / struct_conn
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _refine_hist.d_res_high / _struct_conn.conn_type_id / _struct_conn.id / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: ORF1a
B: ORF1a
C: Ubiquitin-like protein ISG15
D: Ubiquitin-like protein ISG15
hetero molecules


Theoretical massNumber of molelcules
Total (without water)93,57120
Polymers91,9484
Non-polymers1,62216
Water7,098394
1
A: ORF1a
C: Ubiquitin-like protein ISG15
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,5818
Polymers45,9742
Non-polymers6076
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: ORF1a
D: Ubiquitin-like protein ISG15
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,99012
Polymers45,9742
Non-polymers1,01510
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)148.035, 148.035, 134.189
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number146
Space group name H-MH3

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Components

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Protein , 2 types, 4 molecules ABCD

#1: Protein ORF1a


Mass: 28883.543 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human betacoronavirus 2c EMC/2012 / Gene: orf1ab / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: K4LC41, UniProt: K0BWD0*PLUS
#2: Protein Ubiquitin-like protein ISG15 / Interferon-induced 15 kDa protein / Interferon-induced 17 kDa protein / IP17 / Ubiquitin cross- ...Interferon-induced 15 kDa protein / Interferon-induced 17 kDa protein / IP17 / Ubiquitin cross-reactive protein / hUCRP


Mass: 17090.586 Da / Num. of mol.: 2 / Mutation: C78S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ISG15, G1P2, UCRP / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P05161

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Non-polymers , 7 types, 410 molecules

#3: Chemical
ChemComp-PGE / TRIETHYLENE GLYCOL


Mass: 150.173 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C6H14O4
#4: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#5: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C3H8O3
#6: Chemical ChemComp-AYE / prop-2-en-1-amine / ALLYLAMINE


Mass: 57.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H7N
#7: Chemical ChemComp-CIT / CITRIC ACID


Mass: 192.124 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C6H8O7
#8: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6O2
#9: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 394 / Source method: isolated from a natural source / Formula: H2O

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 3.1 Å3/Da / Density % sol: 60.36 %
Crystal growTemperature: 293.15 K / Method: vapor diffusion, sitting drop / pH: 8.3 / Details: 0.25 M Potassium Citrate, pH 8.3 20% PEG3350

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 0.978 Å
DetectorType: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Jun 10, 2017
RadiationMonochromator: Si (111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.978 Å / Relative weight: 1
ReflectionResolution: 2.291→100 Å / Num. obs: 48452 / % possible obs: 98.6 % / Redundancy: 3.8 % / Biso Wilson estimate: 30.81 Å2 / Rmerge(I) obs: 0.1 / Rpim(I) all: 0.058 / Rrim(I) all: 0.116 / Χ2: 1.759 / Net I/σ(I): 10.9 / Num. measured all: 185967
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
2.291-2.343.60.5623920.7320.3370.6570.64499
2.34-2.383.60.49424330.7680.2970.5790.65698.5
2.38-2.433.50.46724210.790.2810.5480.69397.9
2.43-2.483.30.39723790.8170.2460.470.76995.6
2.48-2.533.10.3623290.8440.2260.4280.895.4
2.53-2.593.50.31923640.8830.190.3730.93298
2.59-2.664.10.28724710.9240.160.330.9699.7
2.66-2.734.10.2624390.9320.1480.31.06999.8
2.73-2.814.10.21624610.950.1210.2491.15499.8
2.81-2.94.10.19224490.9630.1070.2211.35199.8
2.9-34.10.16424440.9660.0920.1891.58299.6
3-3.124.10.1424840.9790.0780.1611.81699.8
3.12-3.264.10.1224360.9840.0670.1382.06799.8
3.26-3.4440.10424590.9870.0590.122.53799.6
3.44-3.6540.08524230.9910.0480.0982.99999.8
3.65-3.933.80.07124550.9930.0410.0823.01499
3.93-4.333.60.05824100.9940.0340.0683.03398.6
4.33-4.963.10.04723170.9960.030.0562.92193.8
4.96-6.244.30.05124530.9960.0270.0582.68299.8
6.24-1004.40.04524330.9970.0240.0512.73199.1

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Processing

Software
NameVersionClassification
PHENIX1.9_1692refinement
SCALEPACKdata scaling
PDB_EXTRACT3.22data extraction
HKL-3000data reduction
PHENIX1.9_1692phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4RF1, 1Z2M

4rf1

1z2m


Resolution: 2.291→42.734 Å / SU ML: 0.27 / Cross valid method: FREE R-VALUE / σ(F): 1.99 / Phase error: 24.56 / Stereochemistry target values: ML / Details: FLAT BULK SOLVENT MODEL
RfactorNum. reflection% reflection
Rfree0.215 2006 4.14 %
Rwork0.1715 --
obs0.1735 48445 98.32 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 138.24 Å2 / Biso mean: 45.2931 Å2 / Biso min: 12.95 Å2
Refinement stepCycle: final / Resolution: 2.291→42.734 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6354 0 228 399 6981
Biso mean--56.2 41.31 -
Num. residues----824
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0136629
X-RAY DIFFRACTIONf_angle_d1.0658957
X-RAY DIFFRACTIONf_chiral_restr0.041024
X-RAY DIFFRACTIONf_plane_restr0.0051129
X-RAY DIFFRACTIONf_dihedral_angle_d15.6642410
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 14

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.291-2.34830.27121360.20843184332095
2.3483-2.41180.26081440.20033337348198
2.4118-2.48270.25451380.19683206334496
2.4827-2.56290.2761420.1953239338197
2.5629-2.65440.25381440.188433473491100
2.6544-2.76070.2591480.1934133561100
2.7607-2.88630.24211430.178333233466100
2.8863-3.03850.23771490.175833863535100
3.0385-3.22880.21911450.17333773522100
3.2288-3.4780.22151430.169433283471100
3.478-3.82780.18741460.15583389353599
3.8278-4.38120.2011450.14923314345998
4.3812-5.51790.15391390.15393236337596
5.5179-42.74140.21781440.17983360350499

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