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4L3C

HLA-A*02:01 binding "YLLMWITQV" at 2.64Å 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.

Information sections

Complex type

Class i with peptide

1. Beta 2 microglobulin
['B', 'D', 'F', 'H', 'J', 'L', 'N', 'P', 'R', 'T', 'V', 'X', 'Z', 'b']
2. Class I alpha
HLA-A*02:01
['A', 'C', 'E', 'G', 'I', 'K', 'M', 'O', 'Q', 'S', 'U', 'W', 'Y', 'a']
3. Peptide
YLLMWITQV
['m', 'i', 'k', 'f', 'l', 'h', 'e', 'n', 'p', 'o', 'c', 'g', 'q', 'j']

Species

Locus / Allele group

HLA-A / HLA-A*02

Publication

Class I Major Histocomapatibility Complex: the Trojan horse for secretion of amyloidogenic ��2-microglobulin.

Halabelian L, Ricagno S, Giorgetti S, Santambrogio C, Barbiroli A, Pellegrino S, Achour A, Grandori R, Marchese L, Raimondi S, Mangione PP, Esposito G, Al-Shawi R, Simons JP, Speck I, Stoppini M, Bolognesi M, Bellotti V
J. Biol. Chem. (2013) [doi:10.1074/jbc.m113.524157]  [pubmed:24338476] 

To form extracellular aggregates, amyloidogenic proteins bypass the intracellular quality control, which normally targets unfolded/aggregated polypeptides. Human D76N β2-microglobulin (β2m) variant is the prototype of unstable and amyloidogenic protein that forms abundant extracellular fibrillar deposits. Here we focus on the role of the class I major histocompatibility complex (MHCI) in the intracellular stabilization of D76N β2m. Using biophysical and structural approaches, we show that the MHCI containing D76N β2m (MHCI76) displays stability, dissociation patterns, and crystal structure comparable with those of the MHCI with wild type β2m. Conversely, limited proteolysis experiments show a reduced protease susceptibility for D76N β2m within the MHCI76 as compared with the free variant, suggesting that the MHCI has a chaperone-like activity in preventing D76N β2m degradation within the cell. Accordingly, D76N β2m is normally assembled in the MHCI and circulates as free plasma species in a transgenic mouse model.

Structure deposition and release

Deposited: 2013-06-05
Released: 2013-12-25
Revised: 2014-02-26

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: YLLMWITQV

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 TYR

TYR7
LYS66
THR163
TYR59
GLU63
MET5
TRP167
PHE33
TYR171
TYR159
 P2 LEU

VAL67
PHE9
TYR99
TYR159
TYR7
HIS70
GLU63
LYS66
MET45
 P3 LEU

TYR99
TYR159
HIS70
LYS66
HIS114
LEU156
 P4 MET

LYS66
 P5 TRP

GLN155
HIS70
 P6 ILE

HIS70
ALA69
HIS74
THR73
ARG97
TYR99
 P7 THR

THR73
ASP77
TRP147
VAL152
ARG97
 P8 GLN

THR73
ASP77
TRP147
THR143
LYS146
VAL76
 P9 VAL

TYR116
LEU81
TRP147
THR80
ASP77
TYR84
THR143
TYR123
LYS146

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

ALA24
VAL34
MET45
GLU63
LYS66
VAL67
TYR7
HIS70
PHE9
TYR99
C Pocket

HIS70
THR73
HIS74
PHE9
ARG97
D Pocket

HIS114
GLN155
LEU156
TYR159
LEU160
TYR99
E Pocket

HIS114
TRP147
VAL152
LEU156
ARG97
F Pocket

TYR116
TYR123
THR143
LYS146
TRP147
ASP77
THR80
LEU81
TYR84
VAL95

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
WSFYLLYYTEFTPTEKNEYACRVNHVTLSQPKIVKWDRDM
2. Class I alpha
HLA-A*02:01
IPD-IMGT/HLA
[ipd-imgt:HLA35266]
        10        20        30        40        50        60
GSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYW
        70        80        90       100       110       120
DGETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDG
       130       140       150       160       170       180
KDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETLQ
       190       200       210       220       230       240
RTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGT
       250       260       270
FQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLRWEP
3. Peptide
YLLMWITQV

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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   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]
  1. 4L3C assembly 1  
  2. 4L3C assembly 10  
  3. 4L3C assembly 11  
  4. 4L3C assembly 12  
  5. 4L3C assembly 13  
  6. 4L3C assembly 14  
  7. 4L3C assembly 2  
  8. 4L3C assembly 3  
  9. 4L3C assembly 4  
  10. 4L3C assembly 5  
  11. 4L3C assembly 6  
  12. 4L3C assembly 7  
  13. 4L3C assembly 8  
  14. 4L3C assembly 9  

Components

MHC Class I alpha chain [cif]
  1. 4L3C assembly 1  
  2. 4L3C assembly 10  
  3. 4L3C assembly 11  
  4. 4L3C assembly 12  
  5. 4L3C assembly 13  
  6. 4L3C assembly 14  
  7. 4L3C assembly 2  
  8. 4L3C assembly 3  
  9. 4L3C assembly 4  
  10. 4L3C assembly 5  
  11. 4L3C assembly 6  
  12. 4L3C assembly 7  
  13. 4L3C assembly 8  
  14. 4L3C assembly 9  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 4L3C assembly 1  
  2. 4L3C assembly 10  
  3. 4L3C assembly 11  
  4. 4L3C assembly 12  
  5. 4L3C assembly 13  
  6. 4L3C assembly 14  
  7. 4L3C assembly 2  
  8. 4L3C assembly 3  
  9. 4L3C assembly 4  
  10. 4L3C assembly 5  
  11. 4L3C assembly 6  
  12. 4L3C assembly 7  
  13. 4L3C assembly 8  
  14. 4L3C assembly 9  
Peptide only [cif]
  1. 4L3C assembly 1  
  2. 4L3C assembly 10  
  3. 4L3C assembly 11  
  4. 4L3C assembly 12  
  5. 4L3C assembly 13  
  6. 4L3C assembly 14  
  7. 4L3C assembly 2  
  8. 4L3C assembly 3  
  9. 4L3C assembly 4  
  10. 4L3C assembly 5  
  11. 4L3C assembly 6  
  12. 4L3C assembly 7  
  13. 4L3C assembly 8  
  14. 4L3C assembly 9  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/4l3c

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


Creative Commons Licence
This work is licensed under a Creative Commons Attribution 4.0 International License.