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PDBsum entry 4pjh
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Immune system
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PDB id
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4pjh
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Contents |
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262 a.a.
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99 a.a.
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192 a.a.
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239 a.a.
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PDB id:
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| Name: |
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Immune system
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Title:
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Structure of human mr1-ac-6-fp in complex with human mait b-g8 tcr
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Structure:
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Major histocompatibility complex class i-related gene protein. Chain: a, c. Fragment: unp residues 23-292. Synonym: mhc class i-related gene protein,class i histocompatibility antigen-like protein. Engineered: yes. Mutation: yes. Beta-2-microglobulin.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: mr1. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m, cdabp0092, hdcma22p. Expression_system_taxid: 562
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Resolution:
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2.00Å
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R-factor:
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0.170
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R-free:
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0.198
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Authors:
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R.W.Birkinshaw,J.Rossjohn
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Key ref:
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S.B.Eckle
et al.
(2014).
A molecular basis underpinning the T cell receptor heterogeneity of mucosal-associated invariant T cells.
J Exp Med,
211,
1585-1600.
PubMed id:
DOI:
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Date:
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12-May-14
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Release date:
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02-Jul-14
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PROCHECK
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Headers
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References
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Q95460
(HMR1_HUMAN) -
Major histocompatibility complex class I-related gene protein from Homo sapiens
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Seq:
Struc:
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341 a.a.
262 a.a.*
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P61769
(B2MG_HUMAN) -
Beta-2-microglobulin from Homo sapiens
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Seq:
Struc:
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119 a.a.
99 a.a.*
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DOI no:
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J Exp Med
211:1585-1600
(2014)
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PubMed id:
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A molecular basis underpinning the T cell receptor heterogeneity of mucosal-associated invariant T cells.
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S.B.Eckle,
R.W.Birkinshaw,
L.Kostenko,
A.J.Corbett,
H.E.McWilliam,
R.Reantragoon,
Z.Chen,
N.A.Gherardin,
T.Beddoe,
L.Liu,
O.Patel,
B.Meehan,
D.P.Fairlie,
J.A.Villadangos,
D.I.Godfrey,
L.Kjer-Nielsen,
J.McCluskey,
J.Rossjohn.
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ABSTRACT
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Mucosal-associated invariant T (MAIT) cells express an invariant T cell receptor
(TCR) α-chain (TRAV1-2 joined to TRAJ33, TRAJ20, or TRAJ12 in humans), which
pairs with an array of TCR β-chains. MAIT TCRs can bind folate- and
riboflavin-based metabolites restricted by the major histocompatibility complex
(MHC)-related class I-like molecule, MR1. However, the impact of MAIT TCR and
MR1-ligand heterogeneity on MAIT cell biology is unclear. We show how a
previously uncharacterized MR1 ligand, acetyl-6-formylpterin (Ac-6-FP), markedly
stabilized MR1, potently up-regulated MR1 cell surface expression, and inhibited
MAIT cell activation. These enhanced properties of Ac-6-FP were attributable to
structural alterations in MR1 that subsequently affected MAIT TCR recognition
via conformational changes within the complementarity-determining region (CDR)
3β loop. Analysis of seven TRBV6-1(+) MAIT TCRs demonstrated how CDR3β
hypervariability impacted on MAIT TCR recognition by altering TCR flexibility
and contacts with MR1 and the Ag itself. Ternary structures of TRBV6-1, TRBV6-4,
and TRBV20(+) MAIT TCRs in complex with MR1 bound to a potent riboflavin-based
antigen (Ag) showed how variations in TRBV gene usage exclusively impacted on
MR1 contacts within a consensus MAIT TCR-MR1 footprint. Moreover, differential
TRAJ gene usage was readily accommodated within a conserved MAIT TCR-MR1-Ag
docking mode. Collectively, MAIT TCR heterogeneity can fine-tune MR1 recognition
in an Ag-dependent manner, thereby modulating MAIT cell recognition.
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