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8yc0

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Current revision

T cell receptor V delta2 V gamma9 in GDN

Structural highlights

8yc0 is a 8 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:	Electron Microscopy, Resolution 4.12Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CD3D_HUMAN Defects in CD3D are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-positive (T(-)B(+)NK(+) SCID) [MIM:608971. A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.^[1]

Function

CD3D_HUMAN The CD3 complex mediates signal transduction.

Publication Abstract from PubMed

Gamma delta (gammadelta) T cells, a unique T cell subgroup, are crucial in various immune responses and immunopathology(1-3). The gammadelta T cell receptor (TCR), generated by gammadelta T cells, recognizes a diverse range of antigens independently of the major histocompatibility complex(2). The gammadelta TCR associates with CD3 subunits, initiating T cell activation and holding great potential in immunotherapy(4). Here, we report the structures of two prototypical human Vgamma9Vdelta2 and Vgamma5Vdelta1 TCR-CD3 complexes(5,6), unveiling two distinct assembly mechanisms that depend on Vgamma usage. The Vgamma9Vdelta2 TCR-CD3 complex is monomeric, with considerable conformational flexibility in the TCRgamma/TCRdelta extracellular domain (ECD) and connecting peptides (CPs). The length of CPs regulates the ligand association and T cell activation. Additionally, a cholesterol-like molecule wedges into the transmembrane region, exerting an inhibitory role in TCR signaling. The Vgamma5Vdelta1 TCR-CD3 complex displays a dimeric architecture, where two protomers nestle back-to-back via their Vgamma5 domains of TCR ECDs. Our biochemical and biophysical assays further corroborate the dimeric structure. Importantly, the dimeric form of the Vgamma5Vdelta1 TCR is essential for T cell activation. These findings reveal organizing principles of the gammadelta TCR-CD3 complex, providing insights into the gammadelta TCR unique properties and facilitating immunotherapeutic interventions.

Structures of human gammadelta T cell receptor-CD3 complex.,Xin W, Huang B, Chi X, Liu Y, Xu M, Zhang Y, Li X, Su Q, Zhou Q Nature. 2024 Apr 24. doi: 10.1038/s41586-024-07439-4. PMID:38657677^[2]

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

References

↑ Dadi HK, Simon AJ, Roifman CM. Effect of CD3delta deficiency on maturation of alpha/beta and gamma/delta T-cell lineages in severe combined immunodeficiency. N Engl J Med. 2003 Nov 6;349(19):1821-8. PMID:14602880 doi:10.1056/NEJMoa031178
↑ Xin W, Huang B, Chi X, Liu Y, Xu M, Zhang Y, Li X, Su Q, Zhou Q. Structures of human γδ T cell receptor-CD3 complex. Nature. 2024 Apr 24. PMID:38657677 doi:10.1038/s41586-024-07439-4

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8yc0"

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 </table>
 == Disease ==
-[https://www.uniprot.org/uniprot/CD3Z_HUMAN CD3Z_HUMAN] Defects in CD247 are the cause of immunodeficiency due to defect in CD3-zeta (CD3ZID) [MIM:[https://omim.org/entry/610163 610163]. An immunological deficiency characterized by T-cells impaired immune response to alloantigens, tetanus toxoid and mitogens.<ref>PMID:16672702</ref>
+[https://www.uniprot.org/uniprot/CD3D_HUMAN CD3D_HUMAN] Defects in CD3D are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-positive (T(-)B(+)NK(+) SCID) [MIM:[https://omim.org/entry/608971 608971]. A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.<ref>PMID:14602880</ref>
 == Function ==
-[https://www.uniprot.org/uniprot/CD3Z_HUMAN CD3Z_HUMAN] Probable role in assembly and expression of the TCR complex as well as signal transduction upon antigen triggering.
+[https://www.uniprot.org/uniprot/CD3D_HUMAN CD3D_HUMAN] The CD3 complex mediates signal transduction.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

8yc0

From Proteopedia

Current revision

T cell receptor V delta2 V gamma9 in GDN

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

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