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- PDB-9pkc: Mur35 Fab with HBV c18V pMHC -

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Basic information

Entry
Database: PDB / ID: 9pkc
TitleMur35 Fab with HBV c18V pMHC
Components
  • Beta-2-microglobulin
  • MHC class I antigen
  • Mur35 Heavy Chain
  • Mur35 Light Chain
  • c18V peptide
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / HBV / pMHC / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


microtubule-dependent intracellular transport of viral material towards nucleus / T=4 icosahedral viral capsid / negative regulation of receptor binding / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / transferrin transport / cellular response to iron ion / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC ...microtubule-dependent intracellular transport of viral material towards nucleus / T=4 icosahedral viral capsid / negative regulation of receptor binding / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / transferrin transport / cellular response to iron ion / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / peptide antigen assembly with MHC class II protein complex / cellular response to iron(III) ion / MHC class II protein complex / negative regulation of forebrain neuron differentiation / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / ER to Golgi transport vesicle membrane / peptide antigen assembly with MHC class I protein complex / regulation of erythrocyte differentiation / regulation of iron ion transport / HFE-transferrin receptor complex / response to molecule of bacterial origin / MHC class I peptide loading complex / T cell mediated cytotoxicity / positive regulation of T cell cytokine production / antigen processing and presentation of endogenous peptide antigen via MHC class I / antigen processing and presentation of exogenous peptide antigen via MHC class II / positive regulation of immune response / MHC class I protein complex / positive regulation of T cell activation / peptide antigen binding / positive regulation of receptor-mediated endocytosis / negative regulation of neurogenesis / cellular response to nicotine / positive regulation of T cell mediated cytotoxicity / multicellular organismal-level iron ion homeostasis / viral penetration into host nucleus / Modulation by Mtb of host immune system / specific granule lumen / phagocytic vesicle membrane / recycling endosome membrane / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / Interferon gamma signaling / negative regulation of epithelial cell proliferation / MHC class II protein complex binding / late endosome membrane / sensory perception of smell / positive regulation of cellular senescence / tertiary granule lumen / DAP12 signaling / T cell differentiation in thymus / ER-Phagosome pathway / host cell / negative regulation of neuron projection development / protein refolding / early endosome membrane / protein homotetramerization / amyloid fibril formation / intracellular iron ion homeostasis / host cell cytoplasm / learning or memory / Amyloid fiber formation / endoplasmic reticulum lumen / Golgi membrane / lysosomal membrane / external side of plasma membrane / focal adhesion / Neutrophil degranulation / symbiont entry into host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / structural molecule activity / endoplasmic reticulum / Golgi apparatus / protein homodimerization activity / extracellular space / DNA binding / RNA binding / extracellular exosome / extracellular region / identical protein binding / membrane / plasma membrane / cytosol
Similarity search - Function
Hepatitis core antigen / Viral capsid core domain supefamily, Hepatitis B virus / Hepatitis core antigen / MHC class I alpha chain, alpha1 alpha2 domains / Class I Histocompatibility antigen, domains alpha 1 and 2 / Beta-2-Microglobulin / : / MHC class I-like antigen recognition-like / MHC class I-like antigen recognition-like superfamily / MHC classes I/II-like antigen recognition protein ...Hepatitis core antigen / Viral capsid core domain supefamily, Hepatitis B virus / Hepatitis core antigen / MHC class I alpha chain, alpha1 alpha2 domains / Class I Histocompatibility antigen, domains alpha 1 and 2 / Beta-2-Microglobulin / : / MHC class I-like antigen recognition-like / MHC class I-like antigen recognition-like superfamily / MHC classes I/II-like antigen recognition protein / : / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Capsid protein / Beta-2-microglobulin / MHC class I antigen
Similarity search - Component
Biological speciesHomo sapiens (human)
Mus musculus (house mouse)
Hepatitis B virus
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 Å
AuthorsMortenson, D.E.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: MAbs / Year: 2025
Title: A highly selective TCR-mimic antibody reveals unexpected mechanisms of HBV peptide-MHC recognition and previously unknown target biology.
Authors: Shahzada Khan / Jeremy Lum / Heather Stephenson / Pawan Bir Kohli / David Mortenson / Dhivya Ramakrishnan / Magdeleine Hung / Sheng Ding / Elbert Seto / Sabrina Lu / Randy Yen / Debi Jin / ...Authors: Shahzada Khan / Jeremy Lum / Heather Stephenson / Pawan Bir Kohli / David Mortenson / Dhivya Ramakrishnan / Magdeleine Hung / Sheng Ding / Elbert Seto / Sabrina Lu / Randy Yen / Debi Jin / Brian Lee / Sheila Clancy / Nicole Schirle Oakdale / Nikolai Novikov / Don Kang / Ruidong Li / David Pan / Rutwij Dave / Eric Lansdon / Simon P Fletcher / Abhishek V Garg / Nathan Thomsen / Scott Balsitis /
Abstract: Curative therapies for chronic hepatitis B virus infection (CHB) are needed, and T-cell redirection is a promising approach, with peptide-MHC complexes (pMHC) being attractive targets. HBV core ...Curative therapies for chronic hepatitis B virus infection (CHB) are needed, and T-cell redirection is a promising approach, with peptide-MHC complexes (pMHC) being attractive targets. HBV core peptide (C18, 10-mer) presented by HLA-A*02:01 (C18-MHC) has two major variants (C18-V or C18-I, differing in the C-terminal residue), both of which are known to be targeted by CD8 T cells in HBV-infected individuals. Through an extensive screening campaign, we identified a highly selective anti-C18-MHC antibody clone MUR35. A MUR35-based T-cell engager (TCE) potently killed HBV-infected hepatocytes but had no activity on uninfected hepatocytes, on other HBV-negative cell types or on host peptides with sequence similarity to C18. Crystal structures of MUR35 bound to both C18-I- and C18-V-MHC revealed a unique binding mode with contacts mediated exclusively by the light chain complementarity-determining regions (CDRs), suggesting that high specificity is achievable without a typical T-cell receptor-like binding mode involving both heavy and light chain CDRs. Although MUR35 exhibits similar binding affinity and structural contacts with C18-V and C18-I, TCE killing was only detected on hepatocytes producing C18-V. To better understand the cause of this discrepancy, we conducted a quantitative proteomics study in an HBV-infected humanized mouse model and found that C18-V was expressed at approximately 300 copies/cell, while C18-I expression was below the limit of detection. Unexpectedly, the proteomics studies revealed that previously unreported 9-mers missing the N-terminal phenylalanine of C18-I and -V were expressed at an average of 508 and 142 copies/cell, respectively, and therefore could be alternative targets for HBV pan genotypic coverage. Our data suggest unexpectedly large differences in antigen presentation efficiency between highly conservative amino acid substitutions in C18 peptide and reveal potentially novel HBV targets for future studies.
History
DepositionJul 14, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 1, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: MHC class I antigen
H: Mur35 Heavy Chain
L: Mur35 Light Chain
P: c18V peptide
B: Beta-2-microglobulin


Theoretical massNumber of molelcules
Total (without water)96,5155
Polymers96,5155
Non-polymers00
Water2,738152
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)72.533, 72.807, 173.429
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP22121
Space group name HallP22ab(z,x,y)
Symmetry operation#1: x,y,z
#2: x,-y,-z
#3: -x,y+1/2,-z+1/2
#4: -x,-y+1/2,z+1/2

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Components

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Protein , 2 types, 2 molecules AB

#1: Protein MHC class I antigen


Mass: 34359.895 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HLA-A / Production host: Escherichia coli (E. coli) / References: UniProt: Q8WLS4
#5: Protein Beta-2-microglobulin


Mass: 11879.356 Da / Num. of mol.: 1 / Fragment: UNP residues 21-119
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: B2M, CDABP0092, HDCMA22P / Production host: Escherichia coli (E. coli) / References: UniProt: P61769

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Antibody , 2 types, 2 molecules HL

#2: Antibody Mur35 Heavy Chain


Mass: 25724.475 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Cell line (production host): expi293 / Production host: Homo sapiens (human)
#3: Antibody Mur35 Light Chain


Mass: 23395.881 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Cell line (production host): expi293 / Production host: Homo sapiens (human)

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Protein/peptide / Non-polymers , 2 types, 153 molecules P

#4: Protein/peptide c18V peptide / Capsid protein / Core antigen / Core protein


Mass: 1155.298 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Hepatitis B virus / References: UniProt: P17391
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 152 / Source method: isolated from a natural source / Formula: H2O

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Details

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: 2.37 Å3/Da / Density % sol: 48.15 %
Crystal growTemperature: 300 K / Method: vapor diffusion, sitting drop / Details: 0.15 M NH4F + 15% PEG3350

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS EIGER2 X 9M / Detector: PIXEL / Date: Feb 15, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.5→72.78 Å / Num. obs: 31246 / % possible obs: 96.7 % / Redundancy: 4.4 % / Biso Wilson estimate: 51.88 Å2 / CC1/2: 0.993 / Rpim(I) all: 0.074 / Rsym value: 0.144 / Net I/σ(I): 7.4
Reflection shellResolution: 2.5→2.6 Å / Mean I/σ(I) obs: 1 / Num. unique obs: 3508 / CC1/2: 0.527 / Rpim(I) all: 0.682 / Rsym value: 1.325

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Processing

Software
NameVersionClassification
PHENIX1.21_5207refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.5→55.76 Å / SU ML: 0.4026 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 33.9369
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.3025 1570 5.04 %
Rwork0.2576 29569 -
obs0.2598 31139 95.36 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 71.43 Å2
Refinement stepCycle: LAST / Resolution: 2.5→55.76 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5914 0 0 152 6066
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00186093
X-RAY DIFFRACTIONf_angle_d0.44218316
X-RAY DIFFRACTIONf_chiral_restr0.039909
X-RAY DIFFRACTIONf_plane_restr0.0041086
X-RAY DIFFRACTIONf_dihedral_angle_d12.66732120
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.5-2.580.36031440.35212559X-RAY DIFFRACTION92.41
2.58-2.670.38771360.32862633X-RAY DIFFRACTION95.58
2.67-2.780.37211420.30042691X-RAY DIFFRACTION97.12
2.78-2.90.36331450.30742735X-RAY DIFFRACTION97.26
2.9-3.060.40231380.30272699X-RAY DIFFRACTION97.26
3.06-3.250.34141430.28062691X-RAY DIFFRACTION96.43
3.25-3.50.32341450.26612684X-RAY DIFFRACTION96.09
3.5-3.850.31831410.25032708X-RAY DIFFRACTION95.67
3.85-4.410.25261430.22712653X-RAY DIFFRACTION94.2
4.41-5.550.24311430.22092695X-RAY DIFFRACTION93.76
5.55-55.760.28991500.24612821X-RAY DIFFRACTION93.46
Refinement TLS params.Method: refined / Origin x: 20.1290539365 Å / Origin y: 17.9399531642 Å / Origin z: 42.3431539249 Å
111213212223313233
T0.357293663005 Å20.00246798711082 Å2-0.0972027995067 Å2-0.21633537175 Å2-0.0280722702066 Å2--0.456941699969 Å2
L2.64094886193 °20.348356848569 °2-1.1938506682 °2-0.595727681388 °2-0.424138228796 °2--1.47964455276 °2
S-0.0712633921177 Å °-0.0125172224757 Å °0.0941328542716 Å °0.00356203596837 Å °0.0101793312275 Å °-0.103712825708 Å °-0.0121154297735 Å °0.168892131108 Å °0.0654117092198 Å °
Refinement TLS groupSelection details: all

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