4x6b

From Proteopedia

Jump to: navigation, search

BK6 TCR apo structure

Structural highlights

4x6b is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.1Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

TRAC_HUMAN TCR-alpha-beta-positive T-cell deficiency. The disease is caused by variants affecting the gene represented in this entry.

Function

TRAC_HUMAN Constant region of T cell receptor (TR) alpha chain (PubMed:24600447). Alpha-beta T cell receptors are antigen specific receptors which are essential to the immune response and are present on the cell surface of T lymphocytes. Recognize peptide-major histocompatibility (MH) (pMH) complexes that are displayed by antigen presenting cells (APC), a prerequisite for efficient T cell adaptive immunity against pathogens (PubMed:25493333). Binding of alpha-beta TR to pMH complex initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn, ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell growth and differentiation (PubMed:23524462). The T cell repertoire is generated in the thymus, by V-(D)-J rearrangement. This repertoire is then shaped by intrathymic selection events to generate a peripheral T cell pool of self-MH restricted, non-autoaggressive T cells. Post-thymic interaction of alpha-beta TR with the pMH complexes shapes TR structural and functional avidity (PubMed:15040585).[1] [2] [3] [4]

Publication Abstract from PubMed

A central paradigm in alphabeta T cell-mediated immunity is the simultaneous co-recognition of antigens and antigen-presenting molecules by the alphabeta T cell antigen receptor (TCR). CD1a presents a broad repertoire of lipid-based antigens. We found that a prototypical autoreactive TCR bound CD1a when it was presenting a series of permissive endogenous ligands, while other lipid ligands were nonpermissive to TCR binding. The structures of two TCR-CD1a-lipid complexes showed that the TCR docked over the A' roof of CD1a in a manner that precluded direct contact with permissive ligands. Nonpermissive ligands indirectly inhibited TCR binding by disrupting the TCR-CD1a contact zone. The exclusive recognition of CD1a by the TCR represents a previously unknown mechanism whereby alphabeta T cells indirectly sense self antigens that are bound to an antigen-presenting molecule.

alphabeta T cell antigen receptor recognition of CD1a presenting self lipid ligands.,Birkinshaw RW, Pellicci DG, Cheng TY, Keller AN, Sandoval-Romero M, Gras S, de Jong A, Uldrich AP, Moody DB, Godfrey DI, Rossjohn J Nat Immunol. 2015 Mar;16(3):258-266. doi: 10.1038/ni.3098. Epub 2015 Feb 2. PMID:25642819[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Loading citation details..
Citations
40 reviews cite this structure
The burgeoning family of unconventional T cells.
Godfrey et al. (2015)
39 more
50 other articles
No citations found

See Also

References

  1. ↑ Nikolich-Zugich J, Slifka MK, Messaoudi I. The many important facets of T-cell repertoire diversity. Nat Rev Immunol. 2004 Feb;4(2):123-32. doi: 10.1038/nri1292. PMID:15040585 doi:http://dx.doi.org/10.1038/nri1292
  2. ↑ Brownlie RJ, Zamoyska R. T cell receptor signalling networks: branched, diversified and bounded. Nat Rev Immunol. 2013 Apr;13(4):257-69. doi: 10.1038/nri3403. PMID:23524462 doi:http://dx.doi.org/10.1038/nri3403
  3. ↑ Lefranc MP. Immunoglobulin and T Cell Receptor Genes: IMGT((R)) and the Birth and Rise of Immunoinformatics. Front Immunol. 2014 Feb 5;5:22. doi: 10.3389/fimmu.2014.00022. eCollection 2014. PMID:24600447 doi:http://dx.doi.org/10.3389/fimmu.2014.00022
  4. ↑ Rossjohn J, Gras S, Miles JJ, Turner SJ, Godfrey DI, McCluskey J. T cell antigen receptor recognition of antigen-presenting molecules. Annu Rev Immunol. 2015;33:169-200. doi: 10.1146/annurev-immunol-032414-112334., Epub 2014 Dec 10. PMID:25493333 doi:http://dx.doi.org/10.1146/annurev-immunol-032414-112334
  5. ↑ Birkinshaw RW, Pellicci DG, Cheng TY, Keller AN, Sandoval-Romero M, Gras S, de Jong A, Uldrich AP, Moody DB, Godfrey DI, Rossjohn J. alphabeta T cell antigen receptor recognition of CD1a presenting self lipid ligands. Nat Immunol. 2015 Mar;16(3):258-266. doi: 10.1038/ni.3098. Epub 2015 Feb 2. PMID:25642819 doi:http://dx.doi.org/10.1038/ni.3098

Contents


PDB ID 4x6b

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/4x6b"
Personal tools