6W9V

Non-classical MHC Class I molecule MR1 with Alpha/Beta T cell receptor at 1.95Å 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

Mr1 with alpha beta tcr

1. Beta 2 microglobulin

['B', 'F']

2. MR1

['A', 'C']

3. T cell receptor alpha
TRAV1

['D']

4. T cell receptor beta
TRBV6

['E']

Information on this structure on STCRdab.

Species

Homo sapiens (Human)

Locus / Allele group

Non-classical MHC Class I molecule

Publication

Absence of mucosal-associated invariant T cells in a person with a homozygous point mutation in MR1.

Howson LJ, Awad W, von Borstel A, Lim HJ, McWilliam HEG, Sandoval-Romero ML, Majumdar S, Hamzeh AR, Andrews TD, McDermott DH, Murphy PM, Le Nours J, Mak JYW, Liu L, Fairlie DP, McCluskey J, Villadangos JA, Cook MC, Turner SJ, Davey MS, Ojaimi S, Rossjohn J

Sci Immunol (2020) 5, [doi:10.1126/sciimmunol.abc9492] [pubmed:32709702]

The role unconventional T cells play in protective immunity in humans is unclear. Mucosal-associated invariant T (MAIT) cells are an unconventional T cell subset restricted to the antigen-presenting molecule MR1. Here, we report the discovery of a patient homozygous for a rare Arg31His (R9H in the mature protein) mutation in MR1 who has a history of difficult-to-treat viral and bacterial infections. MR1R9H was unable to present the potent microbially derived MAIT cell stimulatory ligand. The MR1R9H crystal structure revealed that the stimulatory ligand cannot bind due to the mutation lying within, and causing structural perturbation to, the ligand-binding domain of MR1. While MR1R9H could bind and be up-regulated by a MAIT cell inhibitory ligand, the patient lacked circulating MAIT cells. This shows the importance of the stimulatory ligand for MAIT cell selection in humans. The patient had an expanded γδ T cell population, indicating a compensatory interplay between these unconventional T cell subsets.

Structure deposition and release

Deposited: 2020-03-23

Released: 2020-08-05

Revised: 2020-09-30

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 MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD 70 80 90 WSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. MR1 MR1	10 20 30 40 50 60 MRTHSLRYFHLGVSDPIHGVPEFISVGYVDSHPITTYDSVTRQKEPRAPWMAENLAPDHW 70 80 90 100 110 120 ERYTQLLRGWQQMFKVELKRLQRHYNHSGSHTYQRMIGCELLEDGSTTGFLQYAYDGQDF 130 140 150 160 170 180 LIFNKDTLSWLAVDNVAHTIKQAWEANQHELLYQKNWLEEECIAWLKRFLEYGKDTLQRT 190 200 210 220 230 240 EPPLVRVNRKETFPGVTALFCKAHGFYPPEIYMTWMKNGEEIVQEIDYGDILPSGDGTYQ 250 260 270 AWASIELDPQSSNLYSCHVEHSGVHMVLQVP

3. T cell receptor alpha T cell receptor alpha TRAV1	10 20 30 40 50 60 MGQNIDQPTEMTATEGAIVQINCTYQTSGFNGLFWYQQHAGEAPTFLSYNVLDGLEEKGR 70 80 90 100 110 120 FSSFLSRSKGYSYLLLKELQMKDSASYLCAVKDSNYQLIWGAGTKLIIKPDIQNPDPAVY 130 140 150 160 170 180 QLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSD 190 200 FACANAFNNSIIPEDTFFPSPESS

4. T cell receptor beta T cell receptor beta TRBV6	10 20 30 40 50 60 MNAGVTQTPKFQVLKTGQSMTLQCAQDMNHNSMYWYRQDPGMGLRLIYYSASEGTTDKGE 70 80 90 100 110 120 VPNGYNVSRLNKREFSLRLESAAPSQTSVYFCASSVWTGEGSGELFFGEGSRLTVLEDLK 130 140 150 160 170 180 NVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLK 190 200 210 220 230 240 EQPALNDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAE AWGRAD

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]

6W9V assembly 1

Components

MHC Class I alpha chain [cif]

6W9V assembly 1

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

6W9V assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/6w9v

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.