5VGE

HLA-C*07:02 binding "RYRPGTVAL" 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.

Complex type

Class i with peptide

1. Beta 2 microglobulin

['B']

2. Class I alpha
HLA-C*07:02

['A']

3. Peptide
RYRPGTVAL

['C']

Species

Homo sapiens (Human)

Locus / Allele group

HLA-C / HLA-C*07

Publication

Structural and regulatory diversity shape HLA-C protein expression levels.

Kaur G, Gras S, Mobbs JI, Vivian JP, Cortes A, Barber T, Kuttikkatte SB, Jensen LT, Attfield KE, Dendrou CA, Carrington M, McVean G, Purcell AW, Rossjohn J, Fugger L

Nat Commun (2017) 8, 15924 [doi:10.1038/ncomms15924] [pubmed:28649982]

Expression of HLA-C varies widely across individuals in an allele-specific manner. This variation in expression can influence efficacy of the immune response, as shown for infectious and autoimmune diseases. MicroRNA binding partially influences differential HLA-C expression, but the additional contributing factors have remained undetermined. Here we use functional and structural analyses to demonstrate that HLA-C expression is modulated not just at the RNA level, but also at the protein level. Specifically, we show that variation in exons 2 and 3, which encode the α1/α2 domains, drives differential expression of HLA-C allomorphs at the cell surface by influencing the structure of the peptide-binding cleft and the diversity of peptides bound by the HLA-C molecules. Together with a phylogenetic analysis, these results highlight the diversity and long-term balancing selection of regulatory factors that modulate HLA-C expression.

Structure deposition and release

Deposited: 2017-04-11

Released: 2017-06-07

Revised: 2017-07-12

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: RYRPGTVAL

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 ARG

TRP167

PHE33

TYR159

GLU58

MET5

ARG62

TYR171

TYR59

TYR7

THR163

GLU63

LYS66

P2 TYR

SER24

SER99

GLU63

LYS66

ARG97

TYR67

PHE22

ASP9

TYR159

TYR7

GLN70

P3 ARG

ARG97

ASP9

TYR159

TYR7

GLN70

LYS66

ASP114

LEU156

SER99

P4 PRO

LYS66

LEU156

GLN70

GLN155

TYR159

P5 GLY

GLN70

GLN155

P6 THR

ALA152

LEU156

GLN70

GLN155

ALA73

LEU147

P7 VAL

LEU147

GLN155

LYS146

ALA150

P8 ALA

VAL76

LYS146

ALA73

LEU147

SER77

P9 LEU

TYR84

SER77

THR143

LYS146

SER116

ALA73

TYR123

LEU95

ASN80

LEU81

ILE124

LEU147

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

MET5

TYR59

GLU63

LYS66

TYR7

B Pocket

SER24

VAL34

GLY45

GLU63

LYS66

TYR67

TYR7

GLN70

ASP9

SER99

C Pocket

GLN70

ALA73

ASP74

ASP9

ARG97

D Pocket

ASP114

GLN155

LEU156

TYR159

LEU160

SER99

E Pocket

ASP114

LEU147

ALA152

LEU156

ARG97

F Pocket

SER116

TYR123

THR143

LYS146

LEU147

SER77

ASN80

LEU81

TYR84

LEU95

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-C07:02 IPD-IMGT/HLA* [ipd-imgt:HLA34910]	10 20 30 40 50 60 GSHSMRYFDTAVSRPGRGEPRFISVGYVDDTQFVRFDSDAASPRGEPRAPWVEQEGPEYW 70 80 90 100 110 120 DRETQKYKRQAQADRVSLRNLRGYYNQSEDGSHTLQRMSGCDLGPDGRLLRGYDQSAYDG 130 140 150 160 170 180 KDYIALNEDLRSWTAADTAAQITQRKLEAARAAEQLRAYLEGTCVEWLRRYLENGKETLQ 190 200 210 220 230 240 RAEPPKTHVTHHPLSDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGT 250 260 270 FQKWAAVVVPSGQEQRYTCHMQHEGLQEPLTLSWEP

3. Peptide	RYRPGTVAL

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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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]

5VGE assembly 1

Components

MHC Class I alpha chain [cif]

5VGE assembly 1

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

5VGE assembly 1

Peptide only [cif]

5VGE assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/5vge

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.