The Structural Pathway of Interleukin 1 (IL-1) Initiated Signaling Reveals Mechanisms of Oncogenic Mutations and SNPs in Inflammation and Cancer

摘要: Interleukin-1 (IL-1) is a large cytokine family closely related to innate immunity and inflammation. IL-1 proteins are key players in signaling pathways such as apoptosis, TLR, MAPK, NLR NF-κB. The pathway also associated with cancer, chronic inflammation increases the risk of tumor development via oncogenic mutations. Here we illustrate that structures interfaces between this bearing mutations may reveal how. Proteins frequently regulated their interactions, which can turn them ON or OFF. We show significantly at adjoining interface regions, abolish (or enhance) protein-protein interaction, making protein constitutively active inactive, if it repressor). combine known complexes those have predicted for pathway, integrate literature information. In reconstructed there 104 interactions whose three dimensional experimentally identified; only 15 experimentally-determined interacting complexes. By predicting throughout PRISM algorithm, structural coverage from 15% 71%. silico mutagenesis comparison binding energies mechanisms how single nucleotide polymorphism (SNP) abrogate increase affinity mutant native partner. Computational mapping on constitute powerful strategy explain activation/inhibition. It help an mutation SNP works.