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- PDB-6x8p: Crystal structure of 3D11 Fab in complex with Plasmodium berghei ... -

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Basic information

Entry
Database: PDB / ID: 6x8p
TitleCrystal structure of 3D11 Fab in complex with Plasmodium berghei circumsporozoite protein NPND peptide
Components
  • 3D11 Fab heavy chain
  • 3D11 Fab light chain
  • NPND peptide
KeywordsIMMUNE SYSTEM / Malaria / Antibody
Function / homology
Function and homology information


positive regulation by symbiont of entry into host / positive regulation of development of symbiont in host / positive regulation of developmental process / adhesion of symbiont to host cell / entry into host cell by a symbiont-containing vacuole / external side of plasma membrane / cytoplasm
Similarity search - Function
Plasmodium circumsporozoite protein / Thrombospondin type 1 domain / Thrombospondin type-1 (TSP1) repeat superfamily / Thrombospondin type-1 (TSP1) repeat profile. / Thrombospondin type 1 repeats / Thrombospondin type-1 (TSP1) repeat
Similarity search - Domain/homology
Circumsporozoite protein
Similarity search - Component
Biological speciesMus musculus (house mouse)
Plasmodium berghei ANKA (eukaryote)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.27 Å
AuthorsThai, E. / Julien, J.P.
Funding support United States, Canada, 5items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)P41GM111244 United States
Department of Energy (DOE, United States)KP1605010 United States
Other privateCIFAR Azrieli Global Scholar program Canada
Other governmentOntario Early Researcher Award program Canada
Other governmentCanada Research Chair program Canada
CitationJournal: Elife / Year: 2020
Title: Structural ordering of the circumsporozoite protein repeats by inhibitory antibody 3D11.
Authors: Iga Kucharska / Elaine Thai / Ananya Srivastava / John L Rubinstein / Régis Pomès / Jean-Philippe Julien /
Abstract: Plasmodium sporozoites express circumsporozoite protein (CSP) on their surface, an essential protein that contains central repeating motifs. Antibodies targeting this region can neutralize infection, ...Plasmodium sporozoites express circumsporozoite protein (CSP) on their surface, an essential protein that contains central repeating motifs. Antibodies targeting this region can neutralize infection, and the partial efficacy of RTS,S/AS01 - the leading malaria vaccine against (Pf) - has been associated with the humoral response against the repeats. Although structural details of antibody recognition of PfCSP have recently emerged, the molecular basis of antibody-mediated inhibition of other Plasmodium species via CSP binding remains unclear. Here, we analyze the structure and molecular interactions of potent monoclonal antibody (mAb) 3D11 binding to CSP (PbCSP) using molecular dynamics simulations, X-ray crystallography, and cryoEM. We reveal that mAb 3D11 can accommodate all subtle variances of the PbCSP repeating motifs, and, upon binding, induces structural ordering of PbCSP through homotypic interactions. Together, our findings uncover common mechanisms of antibody evolution in mammals against the CSP repeats of Plasmodium sporozoites.
History
DepositionJun 1, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 2, 2020Provider: repository / Type: Initial release
Revision 1.1Dec 16, 2020Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name
Revision 1.2Oct 18, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
H: 3D11 Fab heavy chain
L: 3D11 Fab light chain
P: NPND peptide
hetero molecules


Theoretical massNumber of molelcules
Total (without water)48,6679
Polymers48,2953
Non-polymers3726
Water4,666259
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area6220 Å2
ΔGint-18 kcal/mol
Surface area19490 Å2
MethodPISA
Unit cell
Length a, b, c (Å)59.859, 59.859, 235.005
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
Components on special symmetry positions
IDModelComponents
11L-517-

HOH

21L-518-

HOH

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Components

#1: Antibody 3D11 Fab heavy chain


Mass: 22629.295 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human)
#2: Antibody 3D11 Fab light chain


Mass: 23989.838 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human)
#3: Protein/peptide NPND peptide


Mass: 1675.750 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Plasmodium berghei ANKA (eukaryote) / References: UniProt: P23093*PLUS
#4: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C2H6O2
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 259 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN

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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: 2.52 Å3/Da / Density % sol: 51.12 %
Crystal growTemperature: 293.15 K / Method: vapor diffusion
Details: 25% (w/v) PEG 3350, 0.2 M lithium sulfate, 0.1 M Tris pH 8.5

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: NSLS-II / Beamline: 17-ID-1 / Wavelength: 0.979329 Å
DetectorType: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Feb 5, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979329 Å / Relative weight: 1
ReflectionResolution: 2.27→40 Å / Num. obs: 23398 / % possible obs: 99.3 % / Redundancy: 19.1 % / Biso Wilson estimate: 31.96 Å2 / CC1/2: 0.999 / Net I/σ(I): 19
Reflection shellResolution: 2.27→2.37 Å / Num. unique obs: 2556 / CC1/2: 0.935 / % possible all: 94.4

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Processing

Software
NameVersionClassification
PHENIX1.16_3549refinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2EH7

2eh7


Resolution: 2.27→29.69 Å / SU ML: 0.2286 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 20.9903
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2224 1173 5.03 %
Rwork0.1658 22154 -
obs0.1686 23327 99.31 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 35.16 Å2
Refinement stepCycle: LAST / Resolution: 2.27→29.69 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3369 0 24 259 3652
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0063487
X-RAY DIFFRACTIONf_angle_d0.85854748
X-RAY DIFFRACTIONf_chiral_restr0.0514539
X-RAY DIFFRACTIONf_plane_restr0.0048608
X-RAY DIFFRACTIONf_dihedral_angle_d11.07892111
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.27-2.380.2631380.18582595X-RAY DIFFRACTION94.53
2.38-2.50.27021410.20042719X-RAY DIFFRACTION99.97
2.5-2.660.27181460.20012730X-RAY DIFFRACTION99.97
2.66-2.860.24991460.18682744X-RAY DIFFRACTION100
2.86-3.150.2651470.18852777X-RAY DIFFRACTION100
3.15-3.610.23111510.16792770X-RAY DIFFRACTION99.97
3.61-4.540.18421440.13842829X-RAY DIFFRACTION100
4.54-29.690.17831600.14732990X-RAY DIFFRACTION100
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)
12.270907217271.03905547677-1.371916361294.8047459231-1.191515719444.574119346430.03064581251560.0495498401297-0.1105481677350.0417523045291-0.1170670159080.002493415940860.0864403748170.008304184427950.063500395620.1065230492530.0118459746594-0.04120847952240.259566546422-0.03292725210410.18167143441741.7257707577-25.8371968354-68.037221093
22.32705028103-1.37860319503-1.384930175916.698288463682.217582705252.13281007861-0.103602956709-0.0375747072416-0.07429156708840.08969987646580.02856087402660.576849952650.188044094543-0.2333726356450.09223544071070.200936207954-0.0162861431629-0.02243847058570.2249415218820.03919646227460.21168332755832.4503263833-19.255609863-39.2969854287
31.499376250460.366989418390.02195292271922.413846391192.757814652995.698153844030.04301871740710.0456440734280.08900474547310.14127402216-0.05696217252830.01495544702090.03666430854350.03598572848790.006570291018160.150126868922-0.02480494075750.009198195536260.2383012991780.01404816468190.16395641752659.072396909-13.1807607897-63.1880604144
44.115583962062.50401016589-1.101942970384.26192341315-1.330890420322.874763424020.165425116313-0.249224280071-0.09435073012750.30570736394-0.02798523104040.248553342170.1639171732-0.108893111301-0.1310648869690.2103538416780.0137332496170.007182416491980.2017461853980.002169751217390.18500900470443.5291479634-21.0485190338-28.2436051773
58.546138394540.6996936705662.044692437998.646052285172.764274280182.01580982667-0.4836575389770.9625400471290.679452344367-0.732984543853-0.004526454942380.626268901095-0.237413333953-0.5475088317340.4969369822790.329434061305-0.0552024141802-0.03326907287690.4355872864590.06923624071080.22232116376847.8854410189-14.3806326772-80.2369941319
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'H' and (resid 2 through 113 )
2X-RAY DIFFRACTION2chain 'H' and (resid 114 through 216 )
3X-RAY DIFFRACTION3chain 'L' and (resid 1 through 107 )
4X-RAY DIFFRACTION4chain 'L' and (resid 108 through 214 )
5X-RAY DIFFRACTION5chain 'P' and (resid 1 through 15 )

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