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- PDB-6c7y: Crystal structure of inhibitory protein SOCS1 in complex with JAK... -

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Basic information

Entry
Database: PDB / ID: 6c7y
TitleCrystal structure of inhibitory protein SOCS1 in complex with JAK1 kinase domain
Components
  • Suppressor of cytokine signaling 1
  • Tyrosine-protein kinase JAK1
KeywordsSIGNALING PROTEIN / TRANSFERASE/INHIBITOR / Kinase / Kinase Inhibitor / TRANSFERASE-INHIBITOR complex
Function / homology
Function and homology information


: / Interferon gamma signaling / Regulation of IFNG signaling / Interferon alpha/beta signaling / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of CD4-positive, alpha-beta T cell differentiation / negative regulation of CD8-positive, alpha-beta T cell differentiation / regulation of type II interferon-mediated signaling pathway / negative regulation of tyrosine phosphorylation of STAT protein / protein localization to cell-cell junction ...: / Interferon gamma signaling / Regulation of IFNG signaling / Interferon alpha/beta signaling / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of CD4-positive, alpha-beta T cell differentiation / negative regulation of CD8-positive, alpha-beta T cell differentiation / regulation of type II interferon-mediated signaling pathway / negative regulation of tyrosine phosphorylation of STAT protein / protein localization to cell-cell junction / kinase inhibitor activity / interleukin-11-mediated signaling pathway / CCR5 chemokine receptor binding / type III interferon-mediated signaling pathway / T-helper 17 cell lineage commitment / positive regulation of homotypic cell-cell adhesion / Interleukin-9 signaling / Interleukin-21 signaling / interleukin-9-mediated signaling pathway / interleukin-10-mediated signaling pathway / interleukin-4-mediated signaling pathway / interleukin-2-mediated signaling pathway / 1-phosphatidylinositol-3-kinase regulator activity / interleukin-15-mediated signaling pathway / positive regulation of regulatory T cell differentiation / Interleukin-15 signaling / Interleukin-12 signaling / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-35 Signalling / phosphatidylinositol 3-kinase complex / regulation of growth / Interleukin-2 signaling / growth hormone receptor binding / Other interleukin signaling / IFNG signaling activates MAPKs / Interleukin-20 family signaling / interleukin-6-mediated signaling pathway / type I interferon-mediated signaling pathway / Interleukin-6 signaling / fat cell differentiation / positive regulation of sprouting angiogenesis / MAPK3 (ERK1) activation / Interleukin-10 signaling / extrinsic component of cytoplasmic side of plasma membrane / MAPK1 (ERK2) activation / cell surface receptor signaling pathway via JAK-STAT / phosphatidylinositol phosphate biosynthetic process / Regulation of IFNA/IFNB signaling / growth hormone receptor signaling pathway via JAK-STAT / Interleukin receptor SHC signaling / Regulation of IFNG signaling / type II interferon-mediated signaling pathway / Signaling by CSF3 (G-CSF) / negative regulation of insulin receptor signaling pathway / regulation of cytokine production / insulin-like growth factor receptor binding / Interleukin-7 signaling / cellular response to amino acid stimulus / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / Inactivation of CSF3 (G-CSF) signaling / Evasion by RSV of host interferon responses / cytoplasmic side of plasma membrane / cellular response to virus / ISG15 antiviral mechanism / cytokine-mediated signaling pathway / positive regulation of protein localization to nucleus / cytoplasmic ribonucleoprotein granule / Interferon gamma signaling / Interferon alpha/beta signaling / RAF/MAP kinase cascade / protein phosphatase binding / protein tyrosine kinase activity / Interleukin-4 and Interleukin-13 signaling / Potential therapeutics for SARS / cell differentiation / cytoskeleton / intracellular signal transduction / endosome / protein ubiquitination / protein phosphorylation / response to antibiotic / focal adhesion / ubiquitin protein ligase binding / protein kinase binding / SARS-CoV-2 activates/modulates innate and adaptive immune responses / nucleoplasm / ATP binding / nucleus / metal ion binding / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Suppressor of cytokine signalling 1 / SOCS1, SH2 domain / suppressors of cytokine signalling / SOCS box / SOCS box-like domain superfamily / SOCS box domain / SOCS box domain profile. / SOCS_box / Tyrosine-protein kinase, non-receptor Jak1 / : ...Suppressor of cytokine signalling 1 / SOCS1, SH2 domain / suppressors of cytokine signalling / SOCS box / SOCS box-like domain superfamily / SOCS box domain / SOCS box domain profile. / SOCS_box / Tyrosine-protein kinase, non-receptor Jak1 / : / Tyrosine-protein kinase, non-receptor Jak/Tyk2 / JAK, FERM F2 lobe domain / FERM F1 lobe ubiquitin-like domain / JAK1-3/TYK2, pleckstrin homology-like domain / Jak1 pleckstrin homology-like domain / FERM F2 acyl-CoA binding protein-like domain / FERM F1 ubiquitin-like domain / FERM central domain / FERM superfamily, second domain / FERM domain / FERM domain profile. / Band 4.1 domain / Band 4.1 homologues / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / SH2 domain superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
ACETATE ION / ADENOSINE-5'-DIPHOSPHATE / Suppressor of cytokine signaling 1 / Tyrosine-protein kinase JAK1
Similarity search - Component
Biological speciesHomo sapiens (human)
Gallus gallus (chicken)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.499 Å
AuthorsLiau, N.P.D. / Laktyushin, A. / Lucet, I.S. / Murphy, J.M. / Yao, S. / Callaghan, K. / Nicola, N.A. / Kershaw, N.J. / Babon, J.J.
Funding support Australia, 3items
OrganizationGrant numberCountry
National Health and Medical Research Council (NHMRC, Australia)112299 Australia
National Health and Medical Research Council (NHMRC, Australia)1113577 Australia
National Health and Medical Research Council (NHMRC, Australia)361646 Australia
CitationJournal: Nat Commun / Year: 2018
Title: The molecular basis of JAK/STAT inhibition by SOCS1.
Authors: Liau, N.P.D. / Laktyushin, A. / Lucet, I.S. / Murphy, J.M. / Yao, S. / Whitlock, E. / Callaghan, K. / Nicola, N.A. / Kershaw, N.J. / Babon, J.J.
History
DepositionJan 23, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 2, 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 1.2Jan 8, 2020Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Oct 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 / struct_conn / struct_conn_type
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.conn_type_id / _struct_conn.id / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_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 / _struct_conn_type.id
Revision 1.4Nov 15, 2023Group: Data collection / Category: chem_comp_atom / chem_comp_bond / Item: _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_2

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Tyrosine-protein kinase JAK1
B: Suppressor of cytokine signaling 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,8239
Polymers46,1022
Non-polymers7217
Water63135
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: homology
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4530 Å2
ΔGint-30 kcal/mol
Surface area17780 Å2
MethodPISA
Unit cell
Length a, b, c (Å)83.926, 83.926, 161.438
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number92
Space group name H-MP41212

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Components

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Protein , 2 types, 2 molecules AB

#1: Protein Tyrosine-protein kinase JAK1 / Janus kinase 1 / JAK-1


Mass: 32938.691 Da / Num. of mol.: 1 / Fragment: kinase domain (UNP residues 869-1153)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: JAK1, JAK1A, JAK1B / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P23458, non-specific protein-tyrosine kinase
#2: Protein Suppressor of cytokine signaling 1


Mass: 13162.991 Da / Num. of mol.: 1 / Fragment: UNP residues 48-164
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Gallus gallus (chicken) / Gene: SOCS1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: B6RCQ2

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Non-polymers , 5 types, 42 molecules

#3: Chemical ChemComp-ADP / ADENOSINE-5'-DIPHOSPHATE


Mass: 427.201 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H15N5O10P2 / Comment: ADP, energy-carrying molecule*YM
#4: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#5: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H6O2
#6: Chemical ChemComp-ACT / ACETATE ION


Mass: 59.044 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H3O2
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 35 / 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: 3.09 Å3/Da / Density % sol: 60.17 %
Crystal growTemperature: 281 K / Method: vapor diffusion, hanging drop / pH: 7
Details: 100mM HEPES pH 7.0, 14% (w/v) PEG8000, 100mM magnesium acetate, 2mM TCEP

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Data collection

DiffractionMean temperature: 77 K / Ambient temp details: 100
Diffraction sourceSource: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.9537 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Oct 18, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9537 Å / Relative weight: 1
ReflectionResolution: 2.5→40.613 Å / Num. obs: 20768 / % possible obs: 99.9 % / Redundancy: 8.268 % / Biso Wilson estimate: 54.94 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.113 / Rrim(I) all: 0.121 / Χ2: 1.025 / Net I/σ(I): 15.77 / Num. measured all: 171700 / Scaling rejects: 10
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsCC1/2Rrim(I) all% possible all
2.5-2.568.4191.7011.6612595149914960.6071.81499.8
2.56-2.638.5351.551.8512555147114710.6681.651100
2.63-2.718.4991.0932.5812136142814280.7891.164100
2.71-2.798.5560.8363.3711747137313730.8530.89100
2.79-2.898.5060.7053.9711466134813480.890.751100
2.89-2.998.4560.5424.9511078131013100.9360.577100
2.99-3.18.4820.4036.5510594124912490.9560.43100
3.1-3.238.4480.3058.1910298121912190.9710.325100
3.23-3.378.4310.19311.839831116711660.990.20699.9
3.37-3.538.3430.14715.499352112111210.9940.156100
3.53-3.738.3210.10519.878862106510650.9970.112100
3.73-3.958.2780.07924.78460102210220.9980.085100
3.95-4.228.1380.06330.6178299629620.9980.067100
4.22-4.568.0670.05433.8172288978960.9990.05899.9
4.56-57.9620.05136.1366408348340.9990.054100
5-5.597.830.05134.8259987677660.9990.05599.9
5.59-6.457.5550.05233.5151986886880.9980.056100
6.45-7.97.7170.03941.4745225865860.9990.042100
7.9-11.187.3280.02355.05348147547510.025100
11.18-40.6136.2460.02455.7318303072930.9990.02695.4

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Processing

Software
NameVersionClassification
PHENIX1.11.1_2575refinement
PDB_EXTRACT3.24data extraction
XDSdata reduction
XSCALEdata scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entries 6C5X & 3EYH

6c5x

3eyh


Resolution: 2.499→40.613 Å / SU ML: 0.31 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 25.35 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2414 1995 9.64 %
Rwork0.2067 18707 -
obs0.21 20702 99.93 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 203.28 Å2 / Biso mean: 86.2543 Å2 / Biso min: 25.36 Å2
Refinement stepCycle: final / Resolution: 2.499→40.613 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3046 0 45 35 3126
Biso mean--82.77 56.71 -
Num. residues----391
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0013165
X-RAY DIFFRACTIONf_angle_d0.4784283
X-RAY DIFFRACTIONf_chiral_restr0.038474
X-RAY DIFFRACTIONf_plane_restr0.003542
X-RAY DIFFRACTIONf_dihedral_angle_d10.0541881
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 14 / % reflection obs: 100 %

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all
2.4992-2.56170.34741380.306112991437
2.5617-2.6310.33161410.296913161457
2.631-2.70840.32661400.276413141454
2.7084-2.79580.32451380.261912941432
2.7958-2.89570.30231400.270413191459
2.8957-3.01160.29271400.268713031443
3.0116-3.14860.29591400.246313191459
3.1486-3.31450.25991410.245413181459
3.3145-3.52210.24981430.210813371480
3.5221-3.79380.25381420.205513271469
3.7938-4.17520.20781430.178113441487
4.1752-4.77860.19571440.160713631507
4.7786-6.01740.20661470.18813861533
6.0174-40.61870.21911580.183114681626
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
17.3466-1.32650.71338.60725.38085.6607-0.01560.3028-1.3322-2.14360.2763-1.12510.61441.4286-0.23021.67110.4580.26750.98610.05871.1545-1.001623.4682-8.4362
23.93330.4625-1.00783.65390.15573.697-0.1606-0.0966-1.7508-0.62260.1886-0.07821.56640.452-0.1451.18640.18230.0180.45990.10791.0039-15.417728.5703-2.027
33.5070.11340.20934.6465-1.38545.47730.0945-0.1179-0.4156-0.7725-0.01730.26850.6627-0.0372-0.05520.44190.0115-0.0310.31640.04020.3491-21.475445.7901-2.7854
42.55761.0173-2.77972.7306-2.70316.90510.7604-0.47610.35180.0435-0.0206-0.6851-1.71131.3348-0.3491.0289-0.30520.43660.8288-0.15280.7413-1.189366.7876-9.8764
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1(chain A and resid 869:921)A869 - 921
2X-RAY DIFFRACTION2(chain A and resid 922:1030)A922 - 1030
3X-RAY DIFFRACTION3(chain A and resid 1031:1153)A1031 - 1153
4X-RAY DIFFRACTION4(chain B and resid 52:168)B52 - 168

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