The mysterious role of the NLRP9 pyrin domain in inflammasome assembly

Alba, Eva de

doi:10.1002/1873-3468.13889

Cited by 1 publication

(1 citation statement)

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“…It is widely accepted that homo-/hetero- oligomerization of PYDs is critical to the formation of inflammasome complexes. Interestingly, a sensor protein named NLRP9 was discovered to exist as a monomer in vitro [ 27 , 28 , 29 ]. The isolated state of NLRP9, containing an N-terminal PYD and a NACHT domain, is presumed to attribute to the unique structural features of NLRP9 PYD.…”

Section: Introductionmentioning

confidence: 99%

Key Factors Regulating the Interdomain Dynamics May Contribute to the Assembly of ASC

Pineda

Stevens

et al. 2023

Biology

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The canonical ASC domains, PYD and CARD, are interconnected by a lengthy, semi-flexible linker. The molecular basis and purpose of ASC’s highly dynamic feature remain elusive. In this study, all-atom molecular dynamics simulations were utilized to examine the role of the linker and the interdomain dynamics of the ASC monomer. As revealed in the principal component analysis (PCA), the flexible linker enables interdomain dynamics and rotation. The stumbling between domains is partially attributed to the helical portion of N-terminal residues in the linker. Additionally, the linker exhibits a certain structural preference due to the turn-type structural inclination of the N-terminal and the presence of several prolines on the linker. Such structural preferences lead to the unavailability of regions for PYD type I interactions to CARDs, as evidenced by the CARD spatial restraint analysis. In conclusion, the semi-flexible linker introduces functionally relevant interdomain dynamics, potentially enhancing PYD self-assembly and the subsequent assembly of the inflammasome complex.

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Section: Introductionmentioning

confidence: 99%