6IWH

Crystal structure of rhesus macaque MHC class I molecule Mamu-B*05104 complexed with C14-GGGI lipopeptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.175 

wwPDB Validation 3D Report Full Report


This is version 1.0 of the entry. See complete history

Literature

Identification and Structure of an MHC Class I-Encoded Protein with the Potential to PresentN-Myristoylated 4-mer Peptides to T Cells.

Yamamoto, Y.Morita, D.Shima, Y.Midorikawa, A.Mizutani, T.Suzuki, J.Mori, N.Shiina, T.Inoko, H.Tanaka, Y.Mikami, B.Sugita, M.

(2019) J Immunol. 202: 3349-3358

  • DOI: 10.4049/jimmunol.1900087
  • Primary Citation of Related Structures:  

  • PubMed Abstract: 
  • Similar to host proteins, <i>N </i>-myristoylation occurs for viral proteins to dictate their pathological function. However, this lipid-modifying reaction creates a novel class of "lipopeptide" Ags targeted by host CTLs. The primate MHC class I-enc ...

    Similar to host proteins, N -myristoylation occurs for viral proteins to dictate their pathological function. However, this lipid-modifying reaction creates a novel class of "lipopeptide" Ags targeted by host CTLs. The primate MHC class I-encoded protein, Mamu-B*098, was previously shown to bind N -myristoylated 5-mer peptides. Nevertheless, T cells exist that recognize even shorter lipopeptides, and much remains to be elucidated concerning the molecular mechanisms of lipopeptide presentation. We, in this study, demonstrate that the MHC class I allele, Mamu-B*05104, binds the N -myristoylated 4-mer peptide (C14-Gly-Gly-Ala-Ile) derived from the viral Nef protein for its presentation to CTLs. A phylogenetic tree analysis indicates that these classical MHC class I alleles are not closely associated; however, the high-resolution x-ray crystallographic analyses indicate that both molecules share lipid-binding structures defined by the exceptionally large, hydrophobic B pocket to accommodate the acylated glycine (G1) as an anchor. The C-terminal isoleucine (I4) of C14-Gly-Gly-Ala-Ile anchors at the F pocket, which is distinct from that of Mamu-B*098 and is virtually identical to that of the peptide-presenting MHC class I molecule, HLA-B51. The two central amino acid residues (G2 and A3) are only exposed externally for recognition by T cells, and the methyl side chain on A3 constitutes a major T cell epitope, underscoring that the epitopic diversity is highly limited for lipopeptides as compared with that for MHC class I-presented long peptides. These structural features suggest that lipopeptide-presenting MHC class I alleles comprise a distinct MHC class I subset that mediates an alternative pathway for CTL activation.


    Organizational Affiliation

    Laboratory of Cell Regulation and Molecular Network, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.,Laboratory of Applied Structural Biology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan.,Laboratory of Cell Regulation, Institute for Frontier Life and Medical Sciences, Kyoto University, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.,Laboratory of Cell Regulation, Institute for Frontier Life and Medical Sciences, Kyoto University, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; msugita@infront.kyoto-u.ac.jp.,Center for Bioinformatics and Molecular Medicine, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; and.,Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan.,Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan.,Laboratory of Chemical Ecology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa-Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan.




Macromolecules

Find similar proteins by: Sequence  |  Structure

Entity ID: 1
MoleculeChainsSequence LengthOrganismDetails
MHC class I antigen
A
276Macaca mulattaMutation(s): 4 
Gene Names: Mamu-B
Find proteins for B2ZHY7 (Macaca mulatta)
Go to UniProtKB:  B2ZHY7
Entity ID: 2
MoleculeChainsSequence LengthOrganismDetails
Beta-2-microglobulin
B
100Macaca mulattaMutation(s): 0 
Gene Names: B2M
Find proteins for Q6V7J5 (Macaca mulatta)
Go to Gene View: B2M
Go to UniProtKB:  Q6V7J5
Entity ID: 3
MoleculeChainsSequence LengthOrganismDetails
C14-GGGI lipopeptide
C
5N/AMutation(s): 0 
Protein Feature View is not available: No corresponding UniProt sequence found.
Small Molecules
Ligands 2 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
NA
Query on NA

Download SDF File 
Download CCD File 
A, B
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
 Ligand Interaction
EDO
Query on EDO

Download SDF File 
Download CCD File 
A, B
1,2-ETHANEDIOL
ETHYLENE GLYCOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
 Ligand Interaction
Modified Residues  1 Unique
IDChainsTypeFormula2D DiagramParent
MYR
Query on MYR
C
NON-POLYMERC14 H28 O2

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Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.175 
  • Space Group: P 21 21 21
Unit Cell:
Length (Å)Angle (°)
a = 55.103α = 90.00
b = 80.791β = 90.00
c = 106.421γ = 90.00
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
MOLREPphasing
HKL-2000data collection
HKL-2000data scaling

Structure Validation

View Full Validation Report or Ramachandran Plots



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Japan Society for the Promotion of ScienceJapan16K19151
Japan Society for the Promotion of ScienceJapan15J04072
Japan Society for the Promotion of ScienceJapan16K15517
Japan Society for the Promotion of ScienceJapan17H05791

Revision History 

  • Version 1.0: 2019-08-14
    Type: Initial release