Multiple binding sites on the ASC pyrin domain allow self-association and interaction with NLRP3
نویسندگان
چکیده
Background: Pyrin domains (PYDs) mediate the assembly of inflammasome complexes, but PYD interaction modes are not well characterised. Results: Interaction sites were identified on the PYD of the inflammasome adaptor protein, ASC. Conclusion: ASC PYD has multiple binding sites allowing self-association and interaction with binding partners. Significance: Understanding molecular details of inflammasome assembly may lead to development of anti-inflammatory agents.
منابع مشابه
Multiple binding sites on the pyrin domain of ASC protein allow self-association and interaction with NLRP3 protein.
A key process underlying an innate immune response to pathogens or cellular stress is activation of members of the NOD-like receptor family, such as NLRP3, to assemble caspase-1-activating inflammasome complexes. Activated caspase-1 processes proinflammatory cytokines into active forms that mediate inflammation. Activation of the NLRP3 inflammasome is also associated with common diseases includ...
متن کاملASC Pyrin Domain Self-associates and Binds NLRP3 Protein Using Equivalent Binding Interfaces.
Death domain superfamily members typically act as adaptors mediating in the assembly of supramolecular complexes with critical apoptosis and inflammation functions. These modular proteins consist of death domains, death effector domains, caspase recruitment domains, and pyrin domains (PYD). Despite the high structural similarity among them, only homotypic interactions participate in complex for...
متن کاملNLRP3 inflammasome assembly is regulated by phosphorylation of the pyrin domain
NLRP3 is a cytosolic pattern recognition receptor that senses microbes and endogenous danger signals. Upon activation, NLRP3 forms an inflammasome with the adapter ASC, resulting in caspase-1 activation, release of proinflammatory cytokines and cell death. How NLRP3 activation is regulated by transcriptional and posttranslational mechanisms to prevent aberrant activation remains incompletely un...
متن کاملThree-Dimensional Structure of Human NLRP10/PYNOD Pyrin Domain Reveals a Homotypic Interaction Site Distinct from Its Mouse Homologue
NLRPs (Nucleotide-binding domain, leucine-rich repeat and pyrin domain containing proteins) are a family of pattern-recognition receptors (PRRs) that sense intracellular microbial components and endogenous stress signals. NLRP10 (also known as PYNOD) is a unique NLRP member characterized by a lack of the putative ligand-binding leucine-rich repeat domain. Recently, human NLRP10 has been shown t...
متن کاملResveratrol decreases apoptosis and NLRP3 complex expressions in experimental varicocele rat model
Objective(s): Varicocele is an abnormal dilation in the testicular vein, which can cause hypoxia, reactive oxygen species accumulation, elevation in testicular temperature, and promote apoptosis and increase proinflammatory cytokine production. According to the varicocele pathophysiology, it is possible that a group of cytosolic receptors called nucleotide oligomerization domain (NOD)-like rece...
متن کامل