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1RJZ

H2-Kb binding "SEIEFARL" at 2.60Å resolution

Data provenance

Structure downloaded from PDB Europe using the Coordinate Server. Aligned to residues 1-180 of 1HHK2 using the CEALIGN3 function of PyMol4. Chain assigment using a Levenshtein distance5 method using data from the PDBe REST API6. Organism data from PDBe REST API. Data for both of these operations from the Molecules endpoint. Structure visualised with 3DMol7.

Information sections


Complex type

Class i with peptide

1. Beta 2 microglobulin
['B', 'E']
2. Class I alpha
H2-Kb
['A', 'D']
3. Peptide
SEIEFARL
['P', 'Q']

Species


Locus / Allele group


Publication

Structural basis for the restoration of TCR recognition of an MHC allelic variant by peptide secondary anchor substitution.

Miley MJ, Messaoudi I, Metzner BM, Wu Y, Nikolich-Zugich J, Fremont DH
J. Exp. Med. (2004) 200, 1445-54 [doi:10.1084/jem.20040217]  [pubmed:15557346

Major histocompatibility complex (MHC) class I variants H-2K(b) and H-2K(bm8) differ primarily in the B pocket of the peptide-binding groove, which serves to sequester the P2 secondary anchor residue. This polymorphism determines resistance to lethal herpes simplex virus (HSV-1) infection by modulating T cell responses to the immunodominant glycoprotein B(498-505) epitope, HSV8. We studied the molecular basis of these effects and confirmed that T cell receptors raised against K(b)-HSV8 cannot recognize H-2K(bm8)-HSV8. However, substitution of Ser(P2) to Glu(P2) (peptide H2E) reversed T cell receptor (TCR) recognition; H-2K(bm8)-H2E was recognized whereas H-2K(b)-H2E was not. Insight into the structural basis of this discrimination was obtained by determining the crystal structures of all four MHC class I molecules in complex with bound peptide (pMHCs). Surprisingly, we find no concerted pMHC surface differences that can explain the differential TCR recognition. However, a correlation is apparent between the recognition data and the underlying peptide-binding groove chemistry of the B pocket, revealing that secondary anchor residues can profoundly affect TCR engagement through mechanisms distinct from the alteration of the resting state conformation of the pMHC surface.

Structure deposition and release

Deposited: 2003-11-20
Released: 2004-12-14
Revised: 2021-10-27

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication


Peptide details

Length: Octamer (8 amino acids)

Sequence: SEIEFARL

Interactive view
Cutaway side view (static)
Surface top view (static - coloured by atom property)
Cutaway top view (static)

Data provenance

MHC:peptide complexes are visualised using PyMol. The peptide is superimposed on a consistent cutaway slice of the MHC binding cleft (displayed as a grey mesh) which best indicates the binding pockets for the P1/P5/PC positions (side view - pockets A, E, F) and for the P2/P3/PC-2 positions (top view - pockets B, C, D). In some cases peptides will use a different pocket for a specific peptide position (atypical anchoring). On some structures the peptide may appear to sterically clash with a pocket. This is an artefact of picking a standardised slice of the cleft and overlaying the peptide.


Peptide neighbours

P1 SER

THR163
TRP167
LEU5
GLU63
TYR171
TYR159
ARG62
TYR59
LYS66
TYR7
P2 GLU

ALA67
TYR159
LYS66
TYR7
TYR45
ASN70
GLU63
SER24
P3 ILE

LEU156
ASN70
GLN114
ARG155
TYR159
SER99
LYS66
P4 GLU

LYS66
ASN70
ARG155
P5 PHE

ARG155
VAL9
SER99
PHE74
TYR116
SER73
VAL97
ASN70
GLN114
P6 ALA

TRP147
ASP77
GLU152
ARG155
TYR116
P7 ARG

VAL76
TRP147
ASP77
GLN72
THR143
LYS146
SER73
P8 LEU

LEU81
TRP147
ILE95
ASP77
ILE142
THR143
TYR123
LYS146
TYR116
THR80
TYR84

Colour key

Aromatic Hydrophobic Acidic Basic Neutral/polar

Data provenance

Neighbours are calculated by finding residues with atoms within 5Å of each other using BioPython Neighboursearch module. The list of neighbours is then sorted and filtered to inlcude only neighbours where between the peptide and the MHC Class I alpha chain.

Colours selected to match the YRB scheme. [https://www.frontiersin.org/articles/10.3389/fmolb.2015.00056/full]


Binding cleft pockets


Peptide sidechain binding pockets (static)
Peptide terminii and backbone binding residues (static)
A Pocket

TYR159
THR163
TRP167
TYR171
LEU5
TYR59
GLU63
LYS66
TYR7
B Pocket

SER24
VAL34
TYR45
GLU63
LYS66
ALA67
TYR7
ASN70
VAL9
SER99
C Pocket

ASN70
SER73
PHE74
VAL9
VAL97
D Pocket

GLN114
ARG155
LEU156
TYR159
LEU160
SER99
E Pocket

GLN114
TRP147
GLU152
LEU156
VAL97
F Pocket

TYR116
TYR123
THR143
LYS146
TRP147
ASP77
THR80
LEU81
TYR84
ILE95

Colour key

Binds N-terminus Binds P1 backbone Binds P2 backbone Binds PC-1 backbone Binds C-terminus

Data provenance

N-/C-terminus and peptide backbone binding residues are assigned according to previously published information and pockets are assigned according to an adaptation of a previously published set of residues. All numbering is currently that of the 'canonical' structures of human and mouse MHC Class I molecules.

Chain sequences

1. Beta 2 microglobulin
Beta 2 microglobulin
        10        20        30        40        50        60
MIQKTPQIQVYSRHPPENGKPNILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMSFSKD
        70        80        90
WSFYILAHTEFTPTETDTYACRVKHDSMAEPKTVYWDRDM

2. Class I alpha
H2-Kb
        10        20        30        40        50        60
GPHSLRYFVTAVSRPGLGEPRFISVGYVDNTEFVRFDSDAENPRYEPRARWMEQEGPEYW
        70        80        90       100       110       120
ERETQKAKGNEQSFRVDLRTLLGYYNQSKGGSHTIQVISGCEVGSDGRLLRGYQQYAYDG
       130       140       150       160       170       180
CDYIALNEDLKTWTAADMAALITKHKWEQAGEAERLRAYLEGTCVEWLRRYLKNGNATLL
       190       200       210       220       230       240
RTDSPKAHVTHHSRPEDKVTLRCWALGFYPADITLTWQLNGEELIQDMELVETRPAGDGT
       250       260       270
FQKWASVVVPLGKEQYYTCHVYHQGLPEPLTLRWEPPPST

3. Peptide
SEIEFARL


Data provenance

Sequences are retrieved via the Uniprot method of the RSCB REST API. Sequences are then compared to those derived from the PDB file and matched against sequences retrieved from the IPD-IMGT/HLA database for human sequences, or the IPD-MHC database for other species. Mouse sequences are matched against FASTA files from Uniprot. Sequences for the mature extracellular protein (signal petide and cytoplasmic tail removed) are compared to identical length sequences from the datasources mentioned before using either exact matching or Levenshtein distance based matching.


Downloadable data

Data can be downloaded to your local machine from the links below.
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or in the case of JSON formatted files to retrieve it and use it as part of notebooks such as Jupyter or GoogleColab.
Please take note of the data license. Using data from this site assumes that you have read and will comply with the license.

Complete structures

Aligned structures [cif]
  1. 1RJZ assembly 1  
  2. 1RJZ assembly 2  

Components

MHC Class I alpha chain [cif]
  1. 1RJZ assembly 1  
  2. 1RJZ assembly 2  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 1RJZ assembly 1  
  2. 1RJZ assembly 2  
Peptide only [cif]
  1. 1RJZ assembly 1  
  2. 1RJZ assembly 2  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/1rjz

Data license

The data above is made available under a Creative Commons CC-BY 4.0 license. This means you can copy, remix, transform, build upon and redistribute the material, but you must give appropriate credit, provide a link to the license, and indicate if changes were made.
If you use any data downloaded from this site in a publication, please cite 'https://www.histo.fyi/'. A preprint is in preparation.

Footnotes