5VGD

HLA-C*05:01 binding "SAEPVPLQL" at 2.32Å 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*05:01

['A']

3. Peptide
SAEPVPLQL

['C']

Species

Homo sapiens (Human)

Locus / Allele group

HLA-C / HLA-C*05

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: 2017-05-31

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: SAEPVPLQL

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

PHE33

MET5

TYR171

TYR159

TYR7

TRP167

LYS66

GLU63

TYR59

ARG62

P2 ALA

GLU63

TYR99

TYR67

TYR159

TYR7

TYR9

LYS66

P3 GLU

TYR99

TYR9

LYS66

ASN114

TYR159

ARG156

ARG97

P4 PRO

TYR159

ARG69

LYS66

P5 VAL

ARG156

ARG69

P6 PRO

THR73

ARG156

ARG69

ARG97

GLU152

GLN70

LYS66

P7 LEU

GLU152

ASN114

ASP74

ARG97

THR73

TRP133

TRP147

ARG156

GLN70

ASN77

PHE116

P8 GLN

VAL76

LYS80

THR73

TRP147

ASN77

LYS146

GLU152

P9 LEU

LEU95

LYS146

TYR84

THR143

TYR123

ASN77

LYS80

PHE116

LEU81

TRP147

ILE142

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

LEU159

CYS163

LEU167

LEU171

ARG5

TRP59

THR63

TYR66

PHE7

B Pocket

VAL24

GLN34

GLU45

THR63

TYR66

LYS67

PHE7

ALA70

THR9

GLY99

C Pocket

ALA70

ASP73

ARG74

THR9

MET97

D Pocket

GLN114

ARG155

ARG156

LEU159

GLU160

GLY99

E Pocket

GLN114

GLU147

ALA152

ARG156

MET97

F Pocket

ALA116

ILE123

GLN143

TRP146

GLU147

LEU77

LEU80

ARG81

TYR84

GLN95

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-C05:01 IPD-IMGT/HLA* [ipd-imgt:HLA35265]	10 20 30 40 50 60 SHSMRYFYTAVSRPGRGEPRFIAVGYVDDTQFVQFDSDAASPRGEPRAPWVEQEGPEYWD 70 80 90 100 110 120 RETQKYKRQAQTDRVNLRKLRGYYNQSEAGSHTLQRMYGCDLGPDGRLLRGYNQFAYDGK 130 140 150 160 170 180 DYIALNEDLRSWTAADKAAQITQRKWEAAREAEQRRAYLEGTCVEWLRRYLENGKKTLQR 190 200 210 220 230 240 AEHPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTF 250 260 270 QKWAAVVVPSGEEQRYTCHVQHEGLPEPLTLRWGPSS

3. Peptide	SAEPVPLQL

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]

5VGD assembly 1

Components

MHC Class I alpha chain [cif]

5VGD assembly 1

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

5VGD assembly 1

Peptide only [cif]

5VGD assembly 1

Derived data

Data for this page [json]

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

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.