[English] 日本語
Yorodumi
- PDB-8vsj: Engineered peptide-specific binder in complex with HLA-DR1/CLIP -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8vsj
TitleEngineered peptide-specific binder in complex with HLA-DR1/CLIP
Components
  • (HLA class II histocompatibility ...) x 2
  • Class-II-associated invariant chain peptide
  • Superantigen
  • c44H10 Fab heavy chain
  • c44H10 Fab light chain
KeywordsIMMUNE SYSTEM / complex / engineered protein
Function / homology
Function and homology information


negative regulation of peptide secretion / macrophage migration inhibitory factor signaling pathway / NOS2-CD74 complex / MHC class II protein binding, via antigen binding groove / antigen processing and presentation of endogenous antigen / positive regulation of dendritic cell antigen processing and presentation / macrophage migration inhibitory factor binding / negative regulation of T cell differentiation / positive regulation of macrophage migration inhibitory factor signaling pathway / protein trimerization ...negative regulation of peptide secretion / macrophage migration inhibitory factor signaling pathway / NOS2-CD74 complex / MHC class II protein binding, via antigen binding groove / antigen processing and presentation of endogenous antigen / positive regulation of dendritic cell antigen processing and presentation / macrophage migration inhibitory factor binding / negative regulation of T cell differentiation / positive regulation of macrophage migration inhibitory factor signaling pathway / protein trimerization / macrophage migration inhibitory factor receptor complex / positive regulation of cytokine-mediated signaling pathway / myeloid dendritic cell antigen processing and presentation / antigen processing and presentation of endogenous peptide antigen via MHC class II / autolysosome membrane / regulation of T-helper cell differentiation / positive regulation of prostaglandin biosynthetic process / T cell activation involved in immune response / T cell selection / positive regulation of type 2 immune response / positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation / MHC class II receptor activity / host-mediated suppression of symbiont invasion / positive regulation of CD4-positive, alpha-beta T cell activation / negative thymic T cell selection / MHC class II protein binding / antigen processing and presentation of peptide or polysaccharide antigen via MHC class II / negative regulation of mature B cell apoptotic process / positive regulation of kinase activity / positive regulation of memory T cell differentiation / positive regulation of monocyte differentiation / positive thymic T cell selection / vacuole / CD4 receptor binding / cytokine receptor activity / positive regulation of neutrophil chemotaxis / positive regulation of chemokine (C-X-C motif) ligand 2 production / prostaglandin biosynthetic process / positive regulation of macrophage cytokine production / positive regulation of T cell differentiation / transport vesicle membrane / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of macrophage activation / antigen processing and presentation / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / cytokine binding / nitric-oxide synthase binding / negative regulation of DNA damage response, signal transduction by p53 class mediator / polysaccharide binding / : / immunoglobulin mediated immune response / Generation of second messenger molecules / immunological synapse / Co-inhibition by PD-1 / response to type II interferon / T cell receptor binding / positive regulation of chemokine production / positive regulation of B cell proliferation / multivesicular body / protein folding chaperone / MHC class II antigen presentation / lysosomal lumen / negative regulation of cell migration / trans-Golgi network membrane / Cell surface interactions at the vascular wall / positive regulation of interleukin-8 production / lumenal side of endoplasmic reticulum membrane / peptide antigen assembly with MHC class II protein complex / intracellular protein transport / MHC class II protein complex / clathrin-coated endocytic vesicle membrane / ER to Golgi transport vesicle membrane / antigen processing and presentation of exogenous peptide antigen via MHC class II / positive regulation of immune response / positive regulation of T cell activation / peptide antigen binding / positive regulation of interleukin-6 production / positive regulation of T cell mediated cytotoxicity / cognition / positive regulation of protein phosphorylation / positive regulation of fibroblast proliferation / Interferon gamma signaling / MHC class II protein complex binding / endocytic vesicle membrane / late endosome membrane / Downstream TCR signaling / late endosome / amyloid-beta binding / protein-containing complex assembly / early endosome membrane / adaptive immune response / positive regulation of viral entry into host cell / positive regulation of ERK1 and ERK2 cascade / lysosome / positive regulation of canonical NF-kappaB signal transduction / endosome membrane / positive regulation of MAPK cascade / protein stabilization / immune response
Similarity search - Function
Mycoplasma arthritidis-derived mitogen / Superantigen MAM / Mycoplasma arthritidis-derived mitogen, C-terminal / Mycoplasma arthritidis-derived mitogen / MHC class II-associated invariant chain, trimerisation / MHC class II-associated invariant chain/CLIP, MHC II-interacting / MHC class II-associated invariant chain / MHC class II-associated invariant chain, trimerisation domain superfamily / HLA class II histocompatibility antigen, gamma subunit / Class II MHC-associated invariant chain trimerisation domain ...Mycoplasma arthritidis-derived mitogen / Superantigen MAM / Mycoplasma arthritidis-derived mitogen, C-terminal / Mycoplasma arthritidis-derived mitogen / MHC class II-associated invariant chain, trimerisation / MHC class II-associated invariant chain/CLIP, MHC II-interacting / MHC class II-associated invariant chain / MHC class II-associated invariant chain, trimerisation domain superfamily / HLA class II histocompatibility antigen, gamma subunit / Class II MHC-associated invariant chain trimerisation domain / CLIP, MHC2 interacting / : / Thyroglobulin type-1 repeat signature. / Thyroglobulin type-1 / Thyroglobulin type-1 superfamily / Thyroglobulin type-1 repeat / Thyroglobulin type-1 domain profile. / Thyroglobulin type I repeats. / MHC class II, beta chain, N-terminal / Class II histocompatibility antigen, beta domain / Class II histocompatibility antigen, beta domain / MHC class II, alpha chain, N-terminal / Class II histocompatibility antigen, alpha domain / Class II histocompatibility antigen, alpha domain / MHC class II, alpha/beta chain, N-terminal / 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
HLA class II histocompatibility antigen DR beta chain / HLA class II histocompatibility antigen, DR alpha chain / HLA class II histocompatibility antigen gamma chain / Superantigen
Similarity search - Component
Biological speciesHomo sapiens (human)
Metamycoplasma arthritidis (bacteria)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.28 Å
AuthorsJude, K.M. / Yang, X. / Du, H. / Kassardjian, A. / Julien, J.-P. / Huang, P. / Garcia, K.C.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)r01gm147893 United States
CitationJournal: Nat Biotechnol / Year: 2025
Title: A general system for targeting MHC class II-antigen complex via a single adaptable loop.
Authors: Haotian Du / Jingjia Liu / Kevin M Jude / Xinbo Yang / Ying Li / Braxton Bell / Hongli Yang / Audrey Kassardjian / Wyatt Blackson / Ali Mobedi / Udit Parekh / R Andres Parra Sperberg / Jean- ...Authors: Haotian Du / Jingjia Liu / Kevin M Jude / Xinbo Yang / Ying Li / Braxton Bell / Hongli Yang / Audrey Kassardjian / Wyatt Blackson / Ali Mobedi / Udit Parekh / R Andres Parra Sperberg / Jean-Philippe Julien / Elizabeth D Mellins / K Christopher Garcia / Po-Ssu Huang /
Abstract: Major histocompatibility complex class II (MHCII) bound to a peptide antigen mediates interactions between CD4 T cells and antigen-presenting cells. Targeting peptide-MHCII with T cell antigen ...Major histocompatibility complex class II (MHCII) bound to a peptide antigen mediates interactions between CD4 T cells and antigen-presenting cells. Targeting peptide-MHCII with T cell antigen receptors (TCRs) and TCR-like antibodies has shown promise for autoimmune diseases and microbiome tolerance. To develop a general targeting approach, we introduce targeted recognition of antigen-MHC complex reporter for MHCII (TRACeR-II) for the rapid development of peptide-specific MHCII binders. TRACeR-II binders have a small helical bundle scaffold and use a single loop to recognize peptide-MHCII, which offers versatility and enables structural modeling of the interactions to target MHCII antigens. We demonstrate rapid generation of TRACeR-II binders to multiple molecules with affinities in the low-nanomolar to low-micromolar range, comparable to best-in-class TCRs and antibodies. Through computational protein design, we created specific binding sequences in silico from only the sequence of a severe acute respiratory syndrome coronavirus 2 peptide. TRACeR-II provides a straightforward approach to target antigen-MHCII without relying on combinatorial selection on complementarity-determining region loops.
History
DepositionJan 24, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 2, 2024Provider: repository / Type: Initial release
Revision 1.1Oct 23, 2024Group: Data collection / Structure summary
Category: em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update / _pdbx_entry_details.has_protein_modification
Revision 1.2Feb 19, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update
Revision 1.3Oct 29, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year / _citation_author.identifier_ORCID / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: HLA class II histocompatibility antigen, DR alpha chain
B: HLA class II histocompatibility antigen DR beta chain
C: Superantigen
H: c44H10 Fab heavy chain
L: c44H10 Fab light chain
P: Class-II-associated invariant chain peptide
hetero molecules


Theoretical massNumber of molelcules
Total (without water)108,7839
Polymers108,1206
Non-polymers6643
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

-
HLA class II histocompatibility ... , 2 types, 2 molecules AB

#1: Protein HLA class II histocompatibility antigen, DR alpha chain / MHC class II antigen DRA


Mass: 21400.178 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HLA-DRA, HLA-DRA1 / Production host: Homo sapiens (human) / References: UniProt: P01903
#2: Protein HLA class II histocompatibility antigen DR beta chain / HLA-DRB1 protein / MHC class II antigen


Mass: 22324.938 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HLA-DRB1 / Production host: Homo sapiens (human) / References: UniProt: D7RIG0

-
Antibody , 2 types, 2 molecules HL

#4: Antibody c44H10 Fab heavy chain


Mass: 23668.643 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)
#5: Antibody c44H10 Fab light chain


Mass: 23505.068 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)

-
Protein / Protein/peptide / Sugars , 3 types, 5 molecules CP

#3: Protein Superantigen


Mass: 15544.818 Da / Num. of mol.: 1
Mutation: V30C, Q37S, K38I, H39Y, F40L, V41A, Y59D, L72K, L75E, G86D, V88I, D90K, N92G, G93D, delta 94-97, I100V, T110I, I127T, S144C
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Metamycoplasma arthritidis (bacteria) / Production host: Escherichia coli (E. coli) / References: UniProt: Q48898
#6: Protein/peptide Class-II-associated invariant chain peptide / CLIP


Mass: 1676.118 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CD74, DHLAG / Production host: Homo sapiens (human) / References: UniProt: P04233
#7: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

-
Details

Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: Engineered peptide-specific binder in complex with HLA-DR1/CLIP
Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.3
Buffer component
IDConc.NameFormulaBuffer-ID
10.15 Msodium chlorideNaCl1
20.01 MHEPES1
30.01 %fluorinated octylmaltoside1
SpecimenConc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 4 K

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal magnification: 165000 X / Nominal defocus max: 1800 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 60 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 21332 / Details: eer images

-
Processing

EM softwareName: PHENIX / Version: 1.21_5207 / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 18639350 / Details: template based picks
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 2.28 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 3706646 / Num. of class averages: 1 / Symmetry type: POINT
RefinementCross valid method: NONE
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
Displacement parametersBiso mean: 77.98 Å2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00225967
ELECTRON MICROSCOPYf_angle_d0.44698082
ELECTRON MICROSCOPYf_chiral_restr0.0397887
ELECTRON MICROSCOPYf_plane_restr0.00361037
ELECTRON MICROSCOPYf_dihedral_angle_d11.71472243

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more