4ZFZ

Mamu-B*098:08 binding "GGAIS" at 1.76Å 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', 'E', 'H', 'K']

2. Class I alpha
Mamu-B*098:08

['A', 'D', 'G', 'J']

3. Peptide
GGAIS

['C', 'F', 'I', 'L']

Species

Macaca mulatta (rhesus monkey)

Locus / Allele group

MAMU-B / Mamu-B*098

Publication

Crystal structure of the N-myristoylated lipopeptide-bound MHC class I complex.

Morita D, Yamamoto Y, Mizutani T, Ishikawa T, Suzuki J, Igarashi T, Mori N, Shiina T, Inoko H, Fujita H, Iwai K, Tanaka Y, Mikami B, Sugita M

Nat Commun (2016) 7, 10356 [doi:10.1038/ncomms10356] [pubmed:26758274]

The covalent conjugation of a 14-carbon saturated fatty acid (myristic acid) to the amino-terminal glycine residue is critical for some viral proteins to function. This protein lipidation modification, termed N-myristoylation, is targeted by host cytotoxic T lymphocytes (CTLs) that specifically recognize N-myristoylated short peptides; however, the molecular mechanisms underlying lipopeptide antigen (Ag) presentation remain elusive. Here we show that a primate major histocompatibility complex (MHC) class I-encoded protein is capable of binding N-myristoylated 5-mer peptides and presenting them to specific CTLs. A high-resolution X-ray crystallographic analysis of the MHC class I:lipopeptide complex reveals an Ag-binding groove that is elaborately constructed to bind N-myristoylated short peptides rather than prototypic 9-mer peptides. The identification of lipopeptide-specific, MHC class I-restricted CTLs indicates that the widely accepted concept of MHC class I-mediated presentation of long peptides to CTLs may need some modifications to incorporate a novel MHC class I function of lipopeptide Ag presentation.

Structure deposition and release

Deposited: 2015-04-22

Released: 2016-01-13

Revised: 2020-02-19

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication

Peptide details

Length: Pentamer (5 amino acids)

Sequence: GGAIS

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

P2 GLY

THR73

TRP156

ALA70

ASP69

P3 GLY

ASP69

THR73

P4 ALA

THR73

TRP147

SER77

VAL152

P5 ILE

LYS146

THR73

VAL76

ASN80

TRP147

SER77

P6 SER

LEU81

TRP147

ASN142

SER77

ASN80

GLN116

LYS146

THR143

TYR84

TYR123

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

GLU63

ARG66

ARG7

B Pocket

ILE24

PHE34

LYS45

GLU63

ARG66

ARG67

ARG7

ASP70

PHE9

MET99

C Pocket

ASP70

GLN73

THR74

PHE9

GLN97

D Pocket

TYR114

GLU155

GLN156

ALA159

TYR160

MET99

E Pocket

TYR114

LYS147

GLY152

GLN156

GLN97

F Pocket

GLN116

ASP123

ASN143

ARG146

LYS147

VAL77

GLY80

ASN81

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. Beta 2 microglobulin Beta 2 microglobulin	10 20 30 40 50 60 AIQRTPKIQVYSRHPPENGKPNFLNCYVSGFHPSDIEVDLLKNGEKMGKVEHSDLSFSKD 70 80 90 WSFYLLYYTEFTPNEKDEYACRVNHVTLSGPRTVKWDRDM

2. Class I alpha Mamu-B098:08 IPD-MHC* [ipd-mhc:NHP08956]	10 20 30 40 50 60 AGSHSMRYFSTTVSRPGRGEPRFIVVGYVDDTQFVRFDSDAASPKMEPRAPWMEQEGPEY 70 80 90 100 110 120 WEEQTRRVKDAAQTFRVSLGNLRGYYNQSEAGSHTLQTMSGCDLGPDGRLLRGYYQQAYD 130 140 150 160 170 180 GRDYIALNEDLRSWTAADEAAQNTQRKWEAAGVAEQWRAYLEGECLESLRRYLENGKETL 190 200 210 220 230 240 QRAEPPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPGGDG 250 260 270 TFQKWGAVVVPSGEEQRYTCHVQHEGLPEPLTLRWEP

3. Peptide	GGAIS

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.

Clicking on the clipboard icon will copy the url for the data to your clipboard.

This can then be used to load the structure/data directly from the url into an application like PyMol (for 3D structures) using the load command:

e.g. load http://www.histo.fyi/structures/downloads/1hhk_1_peptide.cif

or in the case of JSON formatted files to retrieve it and use it as part of notebooks such as Jupyter or GoogleColab.

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]

Components

MHC Class I alpha chain [cif]

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

Peptide only [cif]

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/4zfz

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.