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- PDB-7zmz: Engineered Interleukin 2 bound to CD25 receptor -

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Basic information

Entry
Database: PDB / ID: 7zmz
TitleEngineered Interleukin 2 bound to CD25 receptor
Components
  • Interleukin-2
  • Interleukin-2 receptor subunit alpha
KeywordsCYTOKINE / CYTOKINE RECEPTOR / PROTEIN ENGINEERING / SIGNALING PROTEIN
Function / homology
Function and homology information


regulation of T cell tolerance induction / interleukin-2 receptor complex / interleukin-2 receptor activity / interleukin-2 binding / kappa-type opioid receptor binding / response to tacrolimus / regulation of T cell homeostatic proliferation / regulation of CD4-positive, alpha-beta T cell proliferation / interleukin-2 receptor binding / negative regulation of lymphocyte proliferation ...regulation of T cell tolerance induction / interleukin-2 receptor complex / interleukin-2 receptor activity / interleukin-2 binding / kappa-type opioid receptor binding / response to tacrolimus / regulation of T cell homeostatic proliferation / regulation of CD4-positive, alpha-beta T cell proliferation / interleukin-2 receptor binding / negative regulation of lymphocyte proliferation / glycosphingolipid binding / positive regulation of plasma cell differentiation / negative regulation of T-helper 17 cell differentiation / activation-induced cell death of T cells / positive regulation of tissue remodeling / RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) / leukocyte activation involved in immune response / positive regulation of isotype switching to IgG isotypes / interleukin-2-mediated signaling pathway / activated T cell proliferation / inflammatory response to antigenic stimulus / cell surface receptor signaling pathway via STAT / kinase activator activity / natural killer cell activation / Interleukin-2 signaling / positive regulation of regulatory T cell differentiation / positive regulation of T cell differentiation / negative regulation of B cell apoptotic process / positive regulation of immunoglobulin production / positive regulation of dendritic spine development / positive regulation of interleukin-17 production / positive regulation of activated T cell proliferation / T cell differentiation / Interleukin receptor SHC signaling / negative regulation of T cell proliferation / Notch signaling pathway / positive regulation of B cell proliferation / extrinsic apoptotic signaling pathway in absence of ligand / cytokine activity / growth factor activity / negative regulation of inflammatory response / positive regulation of type II interferon production / positive regulation of inflammatory response / cell-cell signaling / positive regulation of cytosolic calcium ion concentration / RAF/MAP kinase cascade / carbohydrate binding / positive regulation of cell growth / response to ethanol / phospholipase C-activating G protein-coupled receptor signaling pathway / adaptive immune response / transcription by RNA polymerase II / cell surface receptor signaling pathway / cell adhesion / immune response / inflammatory response / external side of plasma membrane / apoptotic process / positive regulation of cell population proliferation / negative regulation of apoptotic process / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region / plasma membrane
Similarity search - Function
Interleukin-2 receptor alpha / Interleukin-2 / Interleukin-2, conserved site / Interleukin 2 / Interleukin-2 signature. / Interleukin-2 family / Sushi repeat (SCR repeat) / Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR) / Four-helical cytokine-like, core / Sushi/SCR/CCP domain ...Interleukin-2 receptor alpha / Interleukin-2 / Interleukin-2, conserved site / Interleukin 2 / Interleukin-2 signature. / Interleukin-2 family / Sushi repeat (SCR repeat) / Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR) / Four-helical cytokine-like, core / Sushi/SCR/CCP domain / Sushi/CCP/SCR domain profile. / Sushi/SCR/CCP superfamily
Similarity search - Domain/homology
Interleukin-2 receptor subunit alpha / Interleukin-2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.2 Å
AuthorsFyfe, P.K. / Moraga, I. / Gaggero, S. / Mitra, S.
Funding supportEuropean Union, 1items
OrganizationGrant numberCountry
European Research Council (ERC)ERC-206-STGEuropean Union
CitationJournal: Sci Immunol / Year: 2022
Title: IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein.
Authors: Gaggero, S. / Martinez-Fabregas, J. / Cozzani, A. / Fyfe, P.K. / Leprohon, M. / Yang, J. / Thomasen, F.E. / Winkelmann, H. / Magnez, R. / Conti, A.G. / Wilmes, S. / Pohler, E. / van Gijsel ...Authors: Gaggero, S. / Martinez-Fabregas, J. / Cozzani, A. / Fyfe, P.K. / Leprohon, M. / Yang, J. / Thomasen, F.E. / Winkelmann, H. / Magnez, R. / Conti, A.G. / Wilmes, S. / Pohler, E. / van Gijsel Bonnello, M. / Thuru, X. / Quesnel, B. / Soncin, F. / Piehler, J. / Lindorff-Larsen, K. / Roychoudhuri, R. / Moraga, I. / Mitra, S.
History
DepositionApr 20, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Dec 14, 2022Provider: repository / Type: Initial release
Revision 1.1Jan 31, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.2Nov 6, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Interleukin-2
D: Interleukin-2 receptor subunit alpha


Theoretical massNumber of molelcules
Total (without water)45,8382
Polymers45,8382
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1540 Å2
ΔGint-7 kcal/mol
Surface area14610 Å2
MethodPISA
Unit cell
Length a, b, c (Å)89.046, 89.046, 116.683
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number154
Space group name H-MP3221
Space group name HallP322"
Symmetry operation#1: x,y,z
#2: -y,x-y,z+2/3
#3: -x+y,-x,z+1/3
#4: x-y,-y,-z+1/3
#5: -x,-x+y,-z+2/3
#6: y,x,-z

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Components

#1: Protein Interleukin-2 / IL-2 / T-cell growth factor / TCGF


Mass: 16821.375 Da / Num. of mol.: 1 / Mutation: T37H, R38L, T41S, F42Y, K43G
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P60568
#2: Protein Interleukin-2 receptor subunit alpha / IL-2 receptor subunit alpha / IL-2-RA / IL-2R subunit alpha / IL2-RA / TAC antigen / p55


Mass: 29016.316 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IL2RA / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P01589
Has protein modificationY

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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: 4.59 Å3/Da / Density % sol: 73.2 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 6
Details: 19% PEG 3350, 0.2 M Sodium tartrate dibasic dihydrate, 10% glycerol

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9763 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Nov 21, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9763 Å / Relative weight: 1
ReflectionResolution: 3.2→64.33 Å / Num. obs: 9238 / % possible obs: 100 % / Redundancy: 18.4 % / CC1/2: 0.999 / Rmerge(I) obs: 0.233 / Rpim(I) all: 0.078 / Rrim(I) all: 0.246 / Net I/σ(I): 8.3
Reflection shellResolution: 3.2→3.42 Å / Redundancy: 19.1 % / Rmerge(I) obs: 5.973 / Mean I/σ(I) obs: 0.5 / Num. unique obs: 1650 / CC1/2: 0.592 / Rpim(I) all: 1.974 / Rrim(I) all: 6.293 / % possible all: 100

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Processing

Software
NameVersionClassification
PHENIX1.17.1-3660refinement
DIALSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2b5i

2b5i


Resolution: 3.2→64.3 Å / Cross valid method: FREE R-VALUE
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflectionSelection details
Rfree0.258 433 4.7 %Random
Rwork0.237 ---
obs0.238 9148 99.26 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso mean: 147.06 Å2
Refinement stepCycle: LAST / Resolution: 3.2→64.3 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2035 0 0 0 2035
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00652079
X-RAY DIFFRACTIONf_angle_d1.16482808
X-RAY DIFFRACTIONf_chiral_restr0.0561312
X-RAY DIFFRACTIONf_plane_restr0.0061355
X-RAY DIFFRACTIONf_dihedral_angle_d18.0684779
Refinement TLS params.Method: refined / Origin x: -3.5108 Å / Origin y: 34.4197 Å / Origin z: 4.3281 Å
111213212223313233
T1.2285 Å2-0.1289 Å2-0.0175 Å2-1.0059 Å2-0.0095 Å2--0.8805 Å2
L6.4153 °2-2.3767 °2-4.2634 °2-1.3331 °21.4417 °2--5.8585 °2
S-0.0916 Å °0.1944 Å °-0.2006 Å °-0.0251 Å °-0.1498 Å °0.1779 Å °0.0685 Å °-0.6009 Å °0.1524 Å °
Refinement TLS groupSelection details: all

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