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Elucidating the interfaces involved in CARD-CARD interactions mediated by NLRP1 and Caspase-1 using molecular
1Department of Bioinformatics, Orissa University of Agriculture and Technology, Bhubaneswar-751003, Odisha, India.
Abstract:
Inflammasomes are the multi-protein caspase-activating complexes mainly assembled by the sensor proteins (NLRs/ALRs), adaptor molecule (ASC) and effector molecule pro-caspase-1 for the production and release of proinflammatory cytokines, IL-1β and IL-18. NLRP1 is the first NLR known to assemble the multi-protein complex. Unlike NLRP3, NLRP1 has an additional effector binding domain (CARD) at the carboxyl-terminal, which is reported to interact with pro-caspase-1 (precluding the recruitment of ASC) for the transmission of danger signals. So far no direct interaction has been observed between the NLRP1 and CASP1 at the structural level. In this study, an attempt has been made to elucidate the possible mode of interaction(s) between CASP1 and NLRP1 CARDs using structural bioinformatics approaches. The results revealed that the type-Ia patch of CASP1CARD (R10, K11, and R55) is probably the favorable interface for 1:1 interaction. Moreover, the interactions mediated in the type-II and/(or) type-III interfaces of counter CARDs can also be not ruled out altogether. Overall, the findings of this study can be beneficial in understanding the underlying molecular mechanism(s) associated with NLRP1-mediated inflammasome.
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