4CW1

Gaga-BF2*014:01 binding "SWFRKPMTR" at 2.58Å 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.

Complex type

Class i with peptide

1. Beta 2 microglobulin

['B', 'E']

2. Class I alpha
Gaga-BF2*014:01

['A', 'D']

3. Peptide
SWFRKPMTR

['C', 'F']

Species

Gallus gallus (Chicken)

Locus / Allele group

GAGA-BF2 / Gaga-BF2*014

Publication

Expression levels of MHC class I molecules are inversely correlated with promiscuity of peptide binding.

Chappell P, Meziane EK, Harrison M, Magiera ��, Hermann C, Mears L, Wrobel AG, Durant C, Nielsen LL, Buus S, Ternette N, Mwangi W, Butter C, Nair V, Ahyee T, Duggleby R, Madrigal A, Roversi P, Lea SM, Kaufman J

Elife (2015) 4, [doi:10.7554/elife.05345] [pubmed:25860507]

Highly polymorphic major histocompatibility complex (MHC) molecules are at the heart of adaptive immune responses, playing crucial roles in many kinds of disease and in vaccination. We report that breadth of peptide presentation and level of cell surface expression of class I molecules are inversely correlated in both chickens and humans. This relationship correlates with protective responses against infectious pathogens including Marek's disease virus leading to lethal tumours in chickens and human immunodeficiency virus infection progressing to AIDS in humans. We propose that differences in peptide binding repertoire define two groups of MHC class I molecules strategically evolved as generalists and specialists for different modes of pathogen resistance. We suggest that differences in cell surface expression level ensure the development of optimal peripheral T cell responses. The inverse relationship of peptide repertoire and expression is evidently a fundamental property of MHC molecules, with ramifications extending beyond immunology and medicine to evolutionary biology and conservation.

Structure deposition and release

Deposited: 2014-03-31

Released: 2015-05-06

Revised: 2019-02-27

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: SWFRKPMTR

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

TYR58

GLN62

TYR7

TRP164

ILE65

TYR168

TYR156

LEU5

P2 TRP

VAL25

VAL34

VAL66

GLY26

TYR7

ILE65

TYR156

THR24

ASN69

TYR36

VAL43

TYR97

HIS35

GLN9

GLN62

P3 PHE

ASN69

GLY152

ILE65

TYR156

LEU153

TYR97

P4 ARG

GLY61

ASN69

GLN64

ILE65

P5 LYS

GLN9

TRP144

ASN69

LEU95

ILE72

ASP73

P6 PRO

TYR149

P7 MET

LYS143

ILE72

TRP144

TYR149

P8 THR

ASP75

ILE72

TRP144

ASP76

LYS143

P9 ARG

LEU80

VAL93

ASP113

THR79

PRO139

THR140

LYS143

TRP144

LEU95

ARG83

ASP73

PHE120

ASP76

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]

Chain sequences

1. Beta 2 microglobulin Beta 2 microglobulin	10 20 30 40 50 60 DLTPKVQVYSRFPASAGTKNVLNCFAAGFHPPKISITLMKDGVPMEGAQYSDMSFNDDWT 70 80 90 FQRLVHADFTPSSGSTYACKVEHETLKEPQVYKWDPEF

2. Class I alpha Gaga-BF2014:01 IPD-MHC* [ipd-mhc:CHICKEN08575]	10 20 30 40 50 60 ELHTLRYIQTAMTDPGPGQPWFVTVGYVDGELFVHYNSTARRVVPRTEWMAANTDQQYWN 70 80 90 100 110 120 GQTQIVQGNEQIDRDDLGTLQRRYNQTGGSHTVQLMYGCDILEDGTIRGYSQDAYDGRDF 130 140 150 160 170 180 IAFDKGTMTFTAAVPEAVPTKRKWEEGDYAEGLKQYLEETCVEWLRRYVEYGKAELGRRE 190 200 210 220 230 240 RPEVRVWGKEADGILTLSCRAHGFYPRPIVVSWLKDGAVRGQDAQSGGIVPNGDGTYHTW 250 260 270 280 290 300 VTIDAQPGDGDKYQCRVEHASLPQPGLYSWEPRSGGGLNDIFEAQKIEWHENSSSVDKLA AALEHHHHHH

3. Peptide	SWFRKPMTR

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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Complete structures

Aligned structures [cif]

Components

MHC Class I alpha chain [cif]

MHC Class I antigen binding domain (alpha1/alpha2) [cif]

Peptide only [cif]

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/4cw1

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

Protein Data Bank Europe - Coordinate Server
1HHK - HLA-A*02:01 binding LLFGYPVYV at 2.5Å resolution - PDB entry for 1HHK
Protein structure alignment by incremental combinatorial extension (CE) of the optimal path. - PyMol CEALIGN Method - Publication
PyMol - PyMol.org/pymol
Levenshtein distance - Wikipedia entry
Protein Data Bank Europe REST API - Molecules endpoint
3Dmol.js: molecular visualization with WebGL - 3DMol.js - Publication
Protein Data Bank Europe REST API - Publication endpoint
PubMed Central Europe REST API - Articles endpoint

This work is licensed under a Creative Commons Attribution 4.0 International License.