CTLA-4

Function

CTLA4 or Cytotoxic T-Lymphocyte Associated protein 4 is a member of the immunoglobulin superfamily that is expressed by activated T cells and transmits an inhibitory signal to T cells. CTLA4 is homologous to the T-cell co-stimulatory protein, CD28, and both molecules bind to CD80 and CD86, also called B7-1 and B7-2 respectively, on antigen-presenting cells. CTLA-4 binds CD80 and CD86 with greater affinity and avidity than CD28 thus enabling it to outcompete CD28 for its ligands. CTLA4 transmits an inhibitory signal to T cells,[10][11][12][7] whereas CD28 transmits a stimulatory signal.[13][14] CTLA4 is also found in regulatory T cells (Tregs) and contributes to their inhibitory function. T cell activation through the T cell receptor and CD28 leads to increased expression of CTLA-4^[1].

Disease

Variants in this gene have been associated with Type 1 diabetes, Graves' disease, Hashimoto's thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, primary biliary cirrhosis and other autoimmune diseases.

Structural highlights

The protein contains an extracellular V domain, a transmembrane domain, and a cytoplasmic tail. Alternate splice variants, encoding different isoforms, have been characterized. The membrane-bound isoform functions as a homodimer interconnected by a disulfide bond, while the soluble isoform functions as a monomer. The intracellular domain is similar to that of CD28,

3D structures of CTLA-4

Updated on 08-February-2021

2x44, 3osk - hCTLA-4 - human

1ah1 - hCTLA-4 - NMR
5ggv, 5tru, 5xj3, 6rp8, 6xy2 - hCTLA-4 + antibody
6rpj, 6rqm - hCTLA-4 + nanobody
1i8l - hCTLA-4 + CD80
1i85 - hCTLA-4 + CD86
3bx7 - hCTLA-4 + LCN2
7cio - hCTLA-4 + PI3K
4kkn - CTLA-4 - bovine
1dqt, 5e56 - mCTLA-4 - mouse
5e5m - mCTLA-4 + nanobody

References

1. ↑ Fan C, Moews PC, Walsh CT, Knox JR. Vancomycin resistance: structure of D-alanine:D-alanine ligase at 2.3 A resolution. Science. 1994 Oct 21;266(5184):439-43. PMID:7939684

References https://www.wikiwand.com/en/CTLA-4