How does the same ligand activate signaling of different receptors in TNFR superfamily: a computational study.

ABSTRACT: TNFα is a highly pleiotropic cytokine inducing inflammatory signaling pathways. It is initially presented on plasma membrane of cells (mTNFα), and also exists in a soluble variant (sTNFα) after cleavage. The ligand is shared by two structurally similar receptors, TNFR1 and TNFR2. Interestingly, while sTNFα preferentially stimulates TNFR1, TNFR2 signaling can only be activated by mTNFα. How can two similar receptors respond to the same ligand in such a different way? We employed computational simulations in multiple scales to address this question. We found that both mTNFα and sTNFα can trigger the clustering of TNFR1. The size of clusters induced by sTNFα is constantly larger than the clusters induced by mTNFα. The systems of TNFR2, on the other hand, show very different behaviors. Only wh

SUBMITTER: Su Z 

PROVIDER: S-EPMC10409953 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature