Conformational flexibility and inhibitor binding to unphosphorylated interleukin-1 receptor–associated kinase 4 (IRAK4)
نویسندگان
چکیده
منابع مشابه
Structural dynamic analysis of apo and ATP-bound IRAK4 kinase
Interleukin-1 receptor-associated kinases (IRAKs) are Ser/Thr protein kinases that play an important role as signaling mediators in the signal transduction facilitated by the Toll-like receptor (TLR) and interleukin-1 receptor families. Among IRAK family members, IRAK4 is one of the drug targets for diseases related to the TLR and IL-1R signaling pathways. Experimental evidence suggests that th...
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HIV-1 protease remains an important anti-AIDS drug target. Although it has been known that ligand binding induces large conformational changes in the protease, the dynamic aspects of binding have been largely ignored. Several computational models describing protease dynamics have been reported recently. These have reproduced experimental observations, and have also explained how ligands gain ac...
متن کاملIRAK4 Kinase Activation and Cytokine Induction 1 Interleukin 1/Toll-Like Receptor Induced Autophosphorylation Activates Interleukin 1 Receptor- Associated Kinase 4 and Controls Cytokine Induction in a Cell-Type Specific Manner**
IRAK4 is a central kinase in innate immunity but the role of its kinase activity is controversial. The mechanism of activation for IRAK4 is currently unknown; and little is known about the role of IRAK4 kinase in cytokine production, particularly in different human cell types. We show IRAK4 autophosphorylation occurs by an intermolecular reaction and that autophosphorylation is required for ful...
متن کاملFlexibility and conformational entropy in protein-protein binding.
To better understand the interplay between protein-protein binding and protein dynamics, we analyzed molecular dynamics simulations of 17 protein-protein complexes and their unbound components. Complex formation does not restrict the conformational freedom of the partner proteins as a whole, but, rather, it leads to a redistribution of dynamics. We calculate the change in conformational entropy...
متن کاملIRAK4 dimerization and trans-autophosphorylation are induced by Myddosome assembly.
Trans-autophosphorylation is among the most prevalent means of protein kinase activation, yet its molecular basis is poorly defined. In Toll-like receptor and interleukin-1 receptor signaling pathways, the kinase IRAK4 is recruited to the membrane-proximal adaptor MyD88 through death domain (DD) interactions, forming the oligomeric Myddosome and mediating NF-κB activation. Here we show that unp...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2019
ISSN: 0021-9258
DOI: 10.1074/jbc.ra118.005428