6ID4

HLA-A*11:01 binding "AIFQSSMTK" with antibody at 2.40Å 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 and antibody

1. ab_heavy

['H']

2. ab_light

['L']

3. Beta 2 microglobulin

['B', 'F']

4. Class I alpha
HLA-A*11:01

['A', 'E']

5. Peptide
AIFQSSMTK

['T', 'U']

Species

Homo sapiens (Human)

Locus / Allele group

HLA-A / HLA-A*11

Publication

Defining the structural basis for human alloantibody binding to human leukocyte antigen allele HLA-A*11:01.

Gu Y, Wong YH, Liew CW, Chan CEZ, Murali TM, Yap J, Too CT, Purushotorman K, Hamidinia M, El Sahili A, Goh ATH, Teo RZC, Wood KJ, Hanson BJ, Gascoigne NRJ, Lescar J, Vathsala A, MacAry PA

Nat Commun (2019) 10, 893 [doi:10.1038/s41467-019-08790-1] [pubmed:30792391]

Our understanding of the conformational and electrostatic determinants that underlie targeting of human leukocyte antigens (HLA) by anti-HLA alloantibodies is principally based upon in silico modelling. Here we provide a biochemical/biophysical and functional characterization of a human monoclonal alloantibody specific for a common HLA type, HLA-A*11:01. We present a 2.4 Å resolution map of the binding interface of this antibody on HLA-A*11:01 and compare the structural determinants with those utilized by T-cell receptor (TCR), killer-cell immunoglobulin-like receptor (KIR) and CD8 on the same molecule. These data provide a mechanistic insight into the paratope-epitope relationship between an alloantibody and its target HLA molecule in a biological context where other immune receptors are concomitantly engaged. This has important implications for our interpretation of serologic binding patterns of anti-HLA antibodies in sensitized individuals and thus, for the biology of human alloresponses.

Structure deposition and release

Deposited: 2018-09-08

Released: 2019-02-06

Revised: 2020-10-28

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: AIFQSSMTK

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 ALA

ARG163

GLU63

MET5

TYR59

TYR7

TYR171

TYR159

GLN62

TRP167

P2 ILE

ASN66

TYR9

ARG163

GLU63

MET45

TYR7

VAL67

TYR159

TYR99

P3 PHE

TYR99

TYR159

GLN155

ARG163

ARG114

GLN156

TYR9

P4 GLN

ASN66

ARG163

TYR159

P5 SER

GLN155

P6 SER

ARG114

GLN70

THR73

P7 MET

ASP77

GLN155

ARG114

TRP133

TRP147

GLN156

ALA152

THR73

P8 THR

LYS146

TRP147

VAL76

THR73

ASP77

P9 LYS

THR80

ILE142

ARG114

ASP77

THR143

TYR123

LYS146

TRP147

ASP116

ILE124

TYR84

ILE97

LEU81

ILE95

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

ALA159

GLY163

GLU167

ARG171

SER5

GLU59

GLN63

ARG66

ARG7

B Pocket

ILE24

PHE34

ARG45

GLN63

ARG66

ASN67

ARG7

ALA70

PHE9

MET99

C Pocket

ALA70

GLN73

THR74

PHE9

GLN97

D Pocket

TYR114

GLU155

GLN156

ALA159

TYR160

MET99

E Pocket

TYR114

LYS147

HIS152

GLN156

GLN97

F Pocket

GLN116

ASP123

ILE143

ARG146

LYS147

VAL77

GLY80

THR81

GLY84

THR95

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. ab_heavy ab_heavy	10 20 30 40 50 60 EVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTSY 70 80 90 100 110 120 AQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARVTTVIAGPVFDYWGQGTLVTVS 130 140 150 160 170 180 SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS 190 200 210 220 SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPK

2. ab_light ab_light	10 20 30 40 50 60 QAVLTQPSSLSASPGASASLTCTLRSGINVGPYNIYWYQQKPGSPPQYLMRYKSDPDKHQ 70 80 90 100 110 120 GSAVPSRFSGSKDASANAGILLISGLQSEDEADYYCMIWHNNAWVFGGGTKLTVLGQPKA 130 140 150 160 170 180 APSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK 190 200 210 220 YAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS

3. Beta 2 microglobulin Beta 2 microglobulin	10 20 30 40 50 60 MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD 70 80 90 WSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

4. Class I alpha HLA-A11:01 IPD-IMGT/HLA* [ipd-imgt:HLA34732]	10 20 30 40 50 60 MGSHSMRYFYTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEY 70 80 90 100 110 120 WDQETRNVKAQSQTDRVDLGTLRGYYNQSEDGSHTIQIMYGCDVGPDGRFLRGYRQDAYD 130 140 150 160 170 180 GKDYIALNEDLRSWTAADMAAQITKRKWEAAHAAEQQRAYLEGRCVEWLRRYLENGKETL 190 200 210 220 230 240 QRTDPPKTHMTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDG 250 260 270 TFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWE

5. Peptide	AIFQSSMTK

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]

6ID4 assembly 1

Components

MHC Class I alpha chain [cif]

6ID4 assembly 1

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

6ID4 assembly 1

Peptide only [cif]

6ID4 assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/6id4

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.

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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.