7FJE
Cryo-EM structure of a membrane protein(LL)
Summary for 7FJE
| Entry DOI | 10.2210/pdb7fje/pdb |
| EMDB information | 31619 |
| Descriptor | T-cell surface glycoprotein CD3 zeta chain, T-cell surface glycoprotein CD3 delta chain, T-cell surface glycoprotein CD3 epsilon chain, ... (7 entities in total) |
| Functional Keywords | membrane, immune, immune system |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 8 |
| Total formula weight | 189092.75 |
| Authors | |
| Primary citation | Chen, Y.,Zhu, Y.,Li, X.,Gao, W.,Zhen, Z.,Huang, B.,Ma, Z.,Zhang, A.,Song, X.,Ma, Y.,Guo, C.,Zhang, F.,Huang, Z. Cholesterol inhibits TCR signaling by directly restricting TCR-CD3 core tunnel motility. Mol.Cell, 82:1278-1287.e5, 2022 Cited by PubMed Abstract: Cholesterol molecules specifically bind to the resting αβTCR to inhibit cytoplasmic CD3ζ ITAM phosphorylation through sequestering the TCR-CD3 complex in an inactive conformation. The mechanisms of cholesterol-mediated inhibition of TCR-CD3 and its activation remain unclear. Here, we present cryoelectron microscopy structures of cholesterol- and cholesterol sulfate (CS)-inhibited TCR-CD3 complexes and an auto-active TCR-CD3 variant. The structures reveal that cholesterol molecules act like a latch to lock CD3ζ into an inactive conformation in the membrane. Mutations impairing binding of cholesterol molecules to the tunnel result in the movement of the proximal C terminus of the CD3ζ transmembrane helix, thereby activating the TCR-CD3 complex in human cells. Together, our data reveal the structural basis of TCR inhibition by cholesterol, illustrate how the cholesterol-binding tunnel is allosterically coupled to TCR triggering, and lay a foundation for the development of immunotherapies through directly targeting the TCR-CD3 complex. PubMed: 35271814DOI: 10.1016/j.molcel.2022.02.017 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3 Å) |
Structure validation
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