Alpha This is a work in progress and may change. Your feedback is very welcome.
  


7MX4

Non-classical MHC Class I molecule CD1b at 1.73Å 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

Cd1b

1. Beta 2 microglobulin
['B']
2. CD1b
['A']

Species


Locus / Allele group

Non-classical MHC Class I molecule

Publication

Rational design of a hydrolysis-resistant mycobacterial phosphoglycolipid antigen presented by CD1c to T cells.

Reijneveld JF, Marino L, Cao TP, Cheng TY, Dam D, Shahine A, Witte MD, Filippov DV, Suliman S, van der Marel GA, Moody DB, Minnaard AJ, Rossjohn J, Codée JDC, Van Rhijn I
J Biol Chem (2021) 297, 101197 [doi:10.1016/j.jbc.2021.101197]  [pubmed:34536421

Whereas proteolytic cleavage is crucial for peptide presentation by classical major histocompatibility complex (MHC) proteins to T cells, glycolipids presented by CD1 molecules are typically presented in an unmodified form. However, the mycobacterial lipid antigen mannosyl-β1-phosphomycoketide (MPM) may be processed through hydrolysis in antigen presenting cells, forming mannose and phosphomycoketide (PM). To further test the hypothesis that some lipid antigens are processed, and to generate antigens that lead to defined epitopes for future tuberculosis vaccines or diagnostic tests, we aimed to create hydrolysis-resistant MPM variants that retain their antigenicity. Here, we designed and tested three different, versatile synthetic strategies to chemically stabilize MPM analogs. Crystallographic studies of CD1c complexes with these three new MPM analogs showed anchoring of the lipid tail and phosphate group that is highly comparable to nature-identical MPM, with considerable conformational flexibility for the mannose head group. MPM-3, a difluoromethylene-modified version of MPM that is resistant to hydrolysis, showed altered recognition by cells, but not by CD1c proteins, supporting the cellular antigen processing hypothesis. Furthermore, the synthetic analogs elicited T cell responses that were cross-reactive with nature-identical MPM, fulfilling important requirements for future clinical use.

Structure deposition and release

Deposited: 2021-05-18
Released: 2021-11-17
Revised: 2021-11-17

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication


Chain sequences

1. Beta 2 microglobulin
Beta 2 microglobulin
        10        20        30        40        50        60
DAAIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFS
        70        80        90       100
KDWSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDMGSLVPR

2. CD1b
CD1b
        10        20        30        40        50        60
ADASQEHVSFHVIQIFSFVNQSWARGQGSGWLDELQTHGWDSESGTIIFLHQWSKGQFSN
        70        80        90       100       110       120
EELSDLELLFRFYLFGLTREIQDHASQDYSKYPFEVQVKAGCELHSGGSPEGFFQVAFNG
       130       140       150       160       170       180
LDLLSFQQTTWVPSPGCGSLAQSVCHLLNHQYEGVTETVYNLIRSTCPRFLLGLLDAGKM
       190       200       210       220       230       240
YVHRQVRPEAWLSSGPSPGPGRLQLVCHVSGFYPKPVWVMWMRGEQEQQGTQLGDILPNA
       250       260       270       280
NGTWYLRATLDVADGEAAGLSCRVKHSSLEGQDIILYWRGSL


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]
  1. 7MX4 assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 7MX4 assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 7MX4 assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/7mx4

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