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CTLA-4
From Proteopedia
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| + | <StructureSection load='1i8l' size='340' side='right' caption='Human glycosylated CTLA-4 extracellular domain (deepskyblue) complex with CD80 (green) (PDB code [[1i8l]])' scene='83/836584/Cv/1'> | ||
| + | == Function == | ||
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| + | '''CTLA4''' or '''Cytotoxic T-Lymphocyte Associated protein 4''' or '''CD152''' 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<ref>PMID:32185705</ref>. 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. | ||
| - | + | See also [[CTLA4 Gene (Protein Coding) Cytotoxic T-Lymphocyte Associated Protein 4]]. | |
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| - | == Function == | ||
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| - | '''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<ref>PMID:7939684</ref>. | ||
== Disease == | == 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. | + | Variants in this gene have been associated with Type 1 diabetes<ref>PMID:10671941</ref>, Graves' disease, Hashimoto's thyroiditis<ref>PMID:12914522</ref>, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, primary biliary cirrhosis and other autoimmune diseases. |
== Structural highlights == | == 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 | + | 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. <scene name='83/836584/Cv/2'>The complex between CTLA-4 and CD80 is formed mostly by hydrophobic contacts</scene><ref>PMID:11279502</ref>. CTLA-4 residues are shown in ball-and-stick representation, while CD80 residues are in spacefill. |
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| - | </ | + | |
==3D structures of CTLA-4== | ==3D structures of CTLA-4== | ||
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[[2x44]], [[3osk]] - hCTLA-4 - human <br /> | [[2x44]], [[3osk]] - hCTLA-4 - human <br /> | ||
[[1ah1]] - hCTLA-4 - NMR<br /> | [[1ah1]] - hCTLA-4 - NMR<br /> | ||
| - | [[5ggv]], [[5tru]], [[5xj3]], [[6rp8]], [[6xy2]] - hCTLA-4 + antibody <br /> | + | [[5ggv]], [[5tru]], [[5xj3]], [[6rp8]], [[6xy2]], [[7dv4]], [[7elx]], [[7su0]], [[7su1]] - hCTLA-4 + antibody <br /> |
[[6rpj]], [[6rqm]] - hCTLA-4 + nanobody <br /> | [[6rpj]], [[6rqm]] - hCTLA-4 + nanobody <br /> | ||
[[1i8l]] - hCTLA-4 + CD80<br /> | [[1i8l]] - hCTLA-4 + CD80<br /> | ||
Current revision
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