1SYV

HLA-B*44:05 binding "EEFGRAFSF" at 1.70Å 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']

2. Class I alpha
HLA-B*44:05

['A']

3. Peptide
EEFGRAFSF

['C']

Species

Homo sapiens (Human)

Locus / Allele group

HLA-B / HLA-B*44

Publication

Natural HLA class I polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion.

Zernich D, Purcell AW, Macdonald WA, Kjer-Nielsen L, Ely LK, Laham N, Crockford T, Mifsud NA, Bharadwaj M, Chang L, Tait BD, Holdsworth R, Brooks AG, Bottomley SP, Beddoe T, Peh CA, Rossjohn J, McCluskey J

J. Exp. Med. (2004) 200, 13-24 [doi:10.1084/jem.20031680] [pubmed:15226359]

HLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that HLA polymorphism also controls the choice of Ag presentation pathway. A single amino acid polymorphism that distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to constitutively acquire peptides without any detectable incorporation into the transporter associated with Ag presentation (TAP)-associated peptide loading complex even under conditions of extreme peptide starvation. This mode of peptide capture is less susceptible to viral interference than the conventional loading pathway used by HLA-B*4402 that involves assembly of class I molecules within the peptide loading complex. Thus, B*4402 and B*4405 are at opposite extremes of a natural spectrum in HLA class I dependence on the PLC for Ag presentation. These findings unveil a new layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal HLA class I loading versus effective pathogen evasion.

Structure deposition and release

Deposited: 2004-04-02

Released: 2004-10-19

Revised: 2011-07-13

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: EEFGRAFSF

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 GLU

TYR59

TYR7

ARG170

TYR171

LEU163

CYS164

ARG62

GLU63

MET5

SER167

TYR159

P2 GLU

GLU63

ILE66

TYR159

LYS45

SER67

TYR9

TYR99

TYR7

LEU163

ASN70

THR24

P3 PHE

ILE66

GLN155

TYR99

ASP156

TYR159

ARG97

TYR9

P4 GLY

ILE66

P5 ARG

GLN155

ARG97

P6 ALA

THR73

ASN70

P7 PHE

VAL152

GLN155

ASP156

TRP147

ASN77

P8 SER

TRP147

THR73

ASN77

THR143

LYS146

P9 PHE

THR143

TYR123

ILE95

ILE142

LYS146

TYR74

THR80

TYR116

TRP147

ASN77

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

LEU163

SER167

TYR171

MET5

TYR59

GLU63

ILE66

TYR7

B Pocket

THR24

VAL34

LYS45

GLU63

ILE66

SER67

TYR7

ASN70

TYR9

TYR99

C Pocket

ASN70

THR73

TYR74

TYR9

ARG97

D Pocket

ASP114

GLN155

ASP156

TYR159

LEU160

TYR99

E Pocket

ASP114

TRP147

VAL152

ASP156

ARG97

F Pocket

TYR116

TYR123

THR143

LYS146

TRP147

ASN77

THR80

ALA81

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 MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD 70 80 90 WSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha HLA-B44:05 IPD-IMGT/HLA* [ipd-imgt:HLA30859]	10 20 30 40 50 60 GSHSMRYFYTAMSRPGRGEPRFITVGYVDDTLFVRFDSDATSPRKEPRAPWIEQEGPEYW 70 80 90 100 110 120 DRETQISKTNTQTYRENLRTALRYYNQSEAGSHIIQRMYGCDVGPDGRLLRGYDQYAYDG 130 140 150 160 170 180 KDYIALNEDLSSWTAADTAAQITQRKWEAARVAEQDRAYLEGLCVESLRRYLENGKETLQ 190 200 210 220 230 240 RADPPKTHVTHHPISDHEVTLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRT 250 260 270 FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEP

3. Peptide	EEFGRAFSF

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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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]

1SYV assembly 1

Components

MHC Class I alpha chain [cif]

1SYV assembly 1

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

1SYV assembly 1

Peptide only [cif]

1SYV assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/1syv

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.