Structural highlights
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
The T-cell receptor (TCR) initiates T-lymphocyte activation, but mechanistic questions remain( 1-4 ). Here, we present cryogenic electron microscopy structures for the unliganded and human leukocyte antigen (HLA)-bound human TCR-CD3 complex in nanodiscs that provide a native-like lipid environment. Distinct from the "open and extended" conformation seen in detergent( 5-8 ), the unliganded TCR-CD3 in nanodiscs adopts two related "closed and compacted" conformations that represent its physiologic resting state in vivo . By contrast, the HLA-bound complex adopts the open and extended conformation, and conformation-locking disulfide mutants show that ectodomain opening is necessary for maximal ligand-dependent T-cell activation. Together, these results reveal allosteric conformational change during TCR activation and highlight the importance of native-like lipid environments for membrane protein structure determination.
The resting and ligand-bound states of the membrane-embedded human T-cell receptor-CD3 complex.,Notti RQ, Yi F, Heissel S, Bush MW, Molvi Z, Das P, Molina H, Klebanoff CA, Walz T bioRxiv [Preprint]. 2024 Sep 20:2023.08.22.554360. doi: , 10.1101/2023.08.22.554360. PMID:37662363[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
- ↑ Notti RQ, Yi F, Heissel S, Bush MW, Molvi Z, Das P, Molina H, Klebanoff CA, Walz T. The resting and ligand-bound states of the membrane-embedded human T-cell receptor-CD3 complex. bioRxiv [Preprint]. 2024 Sep 20:2023.08.22.554360. PMID:37662363 doi:10.1101/2023.08.22.554360
