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4PGE

H2-Kb binding "FAPGNYPAW" at 2.00Å 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']
2. Class I alpha
H2-Kb
['A']
3. Peptide
FAPGNYPAW
['C']

Species


Locus / Allele group


Publication

The first step of peptide selection in antigen presentation by MHC class I molecules.

Garstka MA, Fish A, Celie PH, Joosten RP, Janssen GM, Berlin I, Hoppes R, Stadnik M, Janssen L, Ovaa H, van Veelen PA, Perrakis A, Neefjes J
Proc. Natl. Acad. Sci. U.S.A. (2015) [doi:10.1073/pnas.1416543112]  [pubmed:25605945

MHC class I molecules present a variable but limited repertoire of antigenic peptides for T-cell recognition. Understanding how peptide selection is achieved requires mechanistic insights into the interactions between the MHC I and candidate peptides. We find that, at first encounter, MHC I H-2K(b) considers a wide range of peptides, including those with expanded N termini and unfitting anchor residues. Discrimination occurs in the second step, when noncanonical peptides dissociate with faster exchange rates. This second step exhibits remarkable temperature sensitivity, as illustrated by numerous noncanonical peptides presented by H-2K(b) in cells cultured at 26 °C relative to 37 °C. Crystallographic analyses of H-2K(b)-peptide complexes suggest that a conformational adaptation of H-2K(b) drives the decisive step in peptide selection. We propose that MHC class I molecules consider initially a large peptide pool, subsequently refined by a temperature-sensitive induced-fit mechanism to retain the canonical peptide repertoire.

Structure deposition and release

Deposited: 2014-05-01
Released: 2015-01-07
Revised: 2020-01-08

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication


Peptide details

Length: Nonamer (9 amino acids)

Sequence: FAPGNYPAW

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 PHE

LYS66
TRP167
PHE33
TYR159
TYR59
TYR7
ARG62
THR163
GLU63
LEU5
TYR171
P2 ALA

GLU63
TYR45
LYS66
TYR159
TYR7
GLU24
P3 PRO

TYR159
TYR7
ASN70
LYS66
SER99
P4 GLY

ASN70
LYS66
P5 ASN

GLU152
ASN70
ARG155
P6 TYR

GLU24
VAL9
GLN114
TYR22
SER73
PHE74
VAL97
TYR116
SER99
TYR7
ASN70
P7 PRO

ASP77
TRP147
GLU152
TYR116
P8 ALA

LYS146
THR143
ASP77
TRP147
P9 TRP

TYR118
ILE95
LYS146
TYR84
TYR123
THR143
PHE74
TYR116
THR80
TRP147
LEU81
ILE142
ASP77
ALA117

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

TRP159
ASP163
LEU167
HIS171
HIS5
PHE59
ASP63
ALA66
HIS7
B Pocket

ASP24
PHE34
GLU45
ASP63
ALA66
GLU67
HIS7
ARG70
HIS9
SER99
C Pocket

ARG70
PRO73
ARG74
HIS9
GLU97
D Pocket

SER114
ASP155
LEU156
TRP159
THR160
SER99
E Pocket

SER114
CYS147
LEU152
LEU156
GLU97
F Pocket

GLY116
VAL123
ALA143
GLY146
CYS147
TRP77
GLN80
GLU81
GLU84
GLY95

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
MGSSHHHHHHSSGLVPRGSHMLEDPMGPHSLRYFVTAVSRPGLGEPRYMEVGYVDDTEFV
        70        80        90       100       110       120
RFDSDAENPRYEPRARWMEQEGPEYWERETQKAKGNEQSFRVDLRTLLGYYNQSKGGSHT
       130       140       150       160       170       180
IQVISGCEVGSDGRLLRGYQQYAYDGCDYIALNEDLKTWTAADMAALITKHKWEQAGEAE
       190       200       210       220       230       240
RLRAYLEGTCVEWLRRYLKNGNATLLRTDSPKAHVTHHSRPEDKVTLRCWALGFYPADIT
       250       260       270       280       290       300
LTWQLNGEELIQDMELVETRPAGDGTFQKWASVVVPLGKEQYYTCHVYHQGLPEPLTLRW

EPPP

3. Peptide
FAPGNYPAW


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

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   e.g. load http://www.histo.fyi/structures/downloads/1hhk_1_peptide.cif
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. 4PGE assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 4PGE assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 4PGE assembly 1  
Peptide only [cif]
  1. 4PGE assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/4pge

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