7BH8

HLA-E*01:03 binding "VMAPRTVLL" with antibody at 1.80Å 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

['E']

2. ab_light

['F']

3. Beta 2 microglobulin

['B', 'D']

4. Class I alpha
HLA-E*01:03

['A', 'C']

5. Peptide
VMAPRTVLL

['P', 'Q']

Species

Homo sapiens (Human)

Locus / Allele group

HLA-E / HLA-E*01

Publication

Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity.

Li D, Brackenridge S, Walters LC, Swanson O, Harlos K, Rozbesky D, Cain DW, Wiehe K, Scearce RM, Barr M, Mu Z, Parks R, Quastel M, Edwards RJ, Wang Y, Rountree W, Saunders KO, Ferrari G, Borrow P, Jones EY, Alam SM, Azoitei ML, Gillespie GM, McMichael AJ, Haynes BF

Commun Biol (2022) 5, 271 [doi:10.1038/s42003-022-03183-5] [pubmed:35347236]

The non-classical class Ib molecule human leukocyte antigen E (HLA-E) has limited polymorphism and can bind HLA class Ia leader peptides (VL9). HLA-E-VL9 complexes interact with the natural killer (NK) cell receptors NKG2A-C/CD94 and regulate NK cell-mediated cytotoxicity. Here we report the isolation of 3H4, a murine HLA-E-VL9-specific IgM antibody that enhances killing of HLA-E-VL9-expressing cells by an NKG2A⁺ NK cell line. Structural analysis reveal that 3H4 acts by preventing CD94/NKG2A docking on HLA-E-VL9. Upon in vitro maturation, an affinity-optimized IgG form of 3H4 showes enhanced NK killing of HLA-E-VL9-expressing cells. HLA-E-VL9-specific IgM antibodies similar in function to 3H4 are also isolated from naïve B cells of cytomegalovirus (CMV)-negative, healthy humans. Thus, HLA-E-VL9-targeting mouse and human antibodies isolated from the naïve B cell antibody pool have the capacity to enhance NK cell cytotoxicity.

Structure deposition and release

Deposited: 2021-01-10

Released: 2022-04-13

Revised: 2022-04-13

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: VMAPRTVLL

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 VAL

THR163

TYR7

TYR171

LEU5

TYR159

TYR59

GLU63

TRP167

P2 MET

TYR159

MET45

ALA67

HIS9

HIS99

GLU63

TYR7

SER24

SER66

THR70

P3 ALA

THR70

GLN156

SER66

TYR159

TRP97

HIS99

P4 PRO

TYR159

ARG62

SER66

P5 ARG

GLN156

ALA150

GLU152

TRP97

HIS155

P6 THR

ILE73

PHE74

PHE116

THR70

GLN156

GLU152

TRP97

P7 VAL

TRP133

ILE73

SER147

GLN156

ASN77

PHE116

GLU152

GLU114

LEU124

P8 LEU

SER147

LYS146

ASN77

GLU152

ILE73

VAL76

P9 LEU

ILE142

LYS146

ASN77

THR80

PHE116

LEU81

LEU124

TYR84

SER143

TYR123

LEU95

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

LEU5

TYR59

GLU63

SER66

TYR7

B Pocket

SER24

VAL34

MET45

GLU63

SER66

ALA67

TYR7

THR70

HIS9

HIS99

C Pocket

THR70

ILE73

PHE74

HIS9

TRP97

D Pocket

GLU114

HIS155

GLN156

TYR159

LEU160

HIS99

E Pocket

GLU114

SER147

GLU152

GLN156

TRP97

F Pocket

PHE116

TYR123

SER143

LYS146

SER147

ASN77

THR80

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. ab_heavy ab_heavy	10 20 30 40 50 60 MGWSCIILFLVATATGVHSEVQLQESGPELVKPGASVKIPCKASGYTFTDYNMDWVKQSH 70 80 90 100 110 120 GKSLEWIGDINPNNGGTIYNQKFKGKATLTVDKSSSTAYMELRSLTSEDTAVYYCARPDY 130 140 150 160 170 180 YGSSYGWYFDVWGTGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT 190 200 210 220 230 240 VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV EPKS

2. ab_light ab_light	10 20 30 40 50 60 MGWSCIILFLVATATGVHSDIVITQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPG 70 80 90 100 110 120 KSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPLTFGAG 130 140 150 160 170 180 TKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQE 190 200 210 220 230 SVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

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

4. Class I alpha HLA-E01:03 IPD-IMGT/HLA* [ipd-imgt:HLA34202]	10 20 30 40 50 60 GSHSLKYFHTSVSRPGRGEPRFISVGYVDDTQFVRFDNDAASPRMVPRAPWMEQEGSEYW 70 80 90 100 110 120 DRETRSARDTAQIFRVNLRTLRGYYNQSEAGSHTLQWMHGCELGPDGRFLRGYEQFAYDG 130 140 150 160 170 180 KDYLTLNEDLRSWTAVDTAAQISEQKSNDASEAEHQRAYLEDTCVEWLHKYLEKGKETLL 190 200 210 220 230 240 HLEPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQQDGEGHTQDTELVETRPAGDGT 250 260 270 FQKWAAVVVPSGEEQRYTCHVQHEGLPEPVTLRWKP

5. Peptide	VMAPRTVLL

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]

7BH8 assembly 1

Components

MHC Class I alpha chain [cif]

7BH8 assembly 1

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

7BH8 assembly 1

Peptide only [cif]

7BH8 assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/7bh8

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.