POP1 might be recruiting its type‐Ia interface for NLRP3‐mediated PYD‐PYD interaction: Insights from MD simulation

Maharana, Jitendra; Vats, Ashutosh; Gautam, Santwana; Nayak, Bibhu Prasad; Kumar, Sushil; Sendha, Jasobanta; De, Sachinandan

doi:10.1002/jmr.2632

Cited by 11 publications

(10 citation statements)

References 46 publications

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“…To observe the self‐association of BcMAVS CARDs , the HuMAVS CARD‐CARD trimer was considered as a template, and a trimeric conformation of the BcMAVS CARD was created using PyMOL (Figure S4). The method and protocol of docking were followed from recent studies on CARD‐CARD interaction …”

Section: Resultsmentioning

confidence: 99%

Structural bioinformatics insights into the CARD‐CARD interaction mediated by the mitochondrial antiviral‐signaling protein of black carp

Rout

Udgata

Dehury

et al. 2019

J of Cellular Biochemistry

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The innate immune system offers the first line of defense against invading microbial pathogens through the recognition of conserved pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). The host innate immune system through PRRs, the sensors for PAMPs, induces the production of cytokines. Among different families of PRRs, the retinoic acidinducible gene I (RIG-I)-like receptors (RLRs), and its mitochondrial adaptor ie, the mitochondrial antiviral-signaling (MAVS) protein, are crucial for RLRtriggered interferon (IFN) antiviral immunity. Recent studies have shown that the N-terminal caspase recruitment domain (CARD) and transmembrane domain play a pivotal role in oligomerization of black carp MAVS (BcMAVS), crucial for the host innate immune response against viral invasion. In this study, we have used molecular modeling, docking, and molecular dynamics (MD) simulation approaches to shed molecular insights into the oligomerization mechanism of BcMAVS CARD . MD simulation and interaction analysis portrayed that the type-I surface patches of BcMAVS CARD make the major contribution to the interaction. Moreover, the evidence from surface patches and critical residues involved in the said interaction is found to be similar to that of the human counterpart and requires further investigation for legitimacy. Altogether, our study provided crucial information on oligomerization of BcMAVS CARDs and might be helpful for clarifying the innate immune response against pathogens and downstream signaling in fishes.

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Section: Resultsmentioning

confidence: 99%

Structural bioinformatics insights into the CARD‐CARD interaction mediated by the mitochondrial antiviral‐signaling protein of black carp

Rout

Udgata

Dehury

et al. 2019

J of Cellular Biochemistry

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“…Thus, the theoretical approaches that include template-assisted molecular modeling, molecular docking, and molecular dynamics simulations are developed for the better understanding of biomolecular machinery and increasingly used to bridge this gap. In recent days, such computational methods have contributed significantly towards the study of the structural and functional aspects of several NLR proteins [69–75] and the protein of interest in this study. In 2012, Zurek et al demonstrated the distinct activation mechanism of NOD1 and NOD2 NACHT and revealed that the mutation of WH-His has contrasting effect on NF-κB signaling mechanism [54].…”

Section: Resultsmentioning

confidence: 99%

Deciphering the ATP-binding mechanism(s) in NLRP-NACHT 3D models using structural bioinformatics approaches

Maharana

Panda

2018

PLoS ONE

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Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs), the first line of defense, are the cytosolic pattern recognition receptors (PRRs) that regulate the inflammatory activity in response to invading pathogens. NLRs are the members of AAA+ ATPase superfamily that comprises of N-terminal EBD(s), a centrally positioned NOD/NACHT and varying range of LRRs towards the C-terminal end. Due to the lack of structural data, the functional aspects of NLRP-signaling mechanism, which includes pathogen recognition, nucleotide-binding, and sensor-adaptor-effector interactions, are not fully understood. In this study, we implemented structural bioinformatics approaches including protein modeling, docking, and molecular dynamics simulations to explore the structural-dynamic features of ADP-/ATP-Mg2+ binding in NLRPNACHT models. Our results indicate a similar mode of ATP-Mg2+ binding in all NLRPNACHT models and the interacting residues are found consistent with reported mutagenesis data. Accompanied by the key amino acids (proposed to be crucial for ATP-Mg2+ coordination), we further have noticed that some additional conserved residues (including ‘Trp’ of the PhhCW motif, and ‘Phe’ and ‘Tyr’ of the GFxxxxRxxYF motif) are potentially interacting with ATP during dynamics; which require further experimentation for legitimacy. Overall, this study will help in understanding the ADP-/ATP-Mg2+ binding mechanisms in NLRPs in a broader perspective and the proposed ATP-binding pocket will aid in designing novel inhibitors for the regulation of inflammasome activity.

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“…The effects of inducer binding in sensor domains were surveyed computationally, including NOD1 LRR interactions with IF-DAP [ 46 ], NOD1 and NOD2 CARD with RIP2 [ 163 , 164 ], and NOD2 MDP binding [ 165 ]. The CARD-CARD interactions of NOD2 were also examined [ 165 ], and additional reports on effector domains have included NLRP3-POP1 PYD-PYD interaction dynamics [ 166 ], NLRP1/Caspase-1 CARD-CARD interactions [ 167 ], and the conformational dynamics and fold stability of NLRP PYDs [ 168 ]. In summary, these domains mediate the homotypic interactions critical for the assembly of filamentous NLR inflammasomes.…”

Section: Structural Basis For Inflammasome Assembly Mechanismsmentioning

confidence: 99%

ATP-Binding and Hydrolysis in Inflammasome Activation

2020

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The prototypical model for NOD-like receptor (NLR) inflammasome assembly includesnucleotide-dependent activation of the NLR downstream of pathogen- or danger-associatedmolecular pattern (PAMP or DAMP) recognition, followed by nucleation of hetero-oligomericplatforms that lie upstream of inflammatory responses associated with innate immunity. Asmembers of the STAND ATPases, the NLRs are generally thought to share a similar model of ATPdependentactivation and effect. However, recent observations have challenged this paradigm toreveal novel and complex biochemical processes to discern NLRs from other STAND proteins. Inthis review, we highlight past findings that identify the regulatory importance of conserved ATPbindingand hydrolysis motifs within the nucleotide-binding NACHT domain of NLRs and explorerecent breakthroughs that generate connections between NLR protein structure and function.Indeed, newly deposited NLR structures for NLRC4 and NLRP3 have provided unique perspectiveson the ATP-dependency of inflammasome activation. Novel molecular dynamic simulations ofNLRP3 examined the active site of ADP- and ATP-bound models. The findings support distinctionsin nucleotide-binding domain topology with occupancy of ATP or ADP that are in turndisseminated on to the global protein structure. Ultimately, studies continue to reveal how the ATPbindingand hydrolysis properties of NACHT domains in different NLRs integrate with signalingmodules and binding partners to control innate immune responses at the molecular level.

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POP1 might be recruiting its type‐Ia interface for NLRP3‐mediated PYD‐PYD interaction: Insights from MD simulation

Cited by 11 publications

References 46 publications

Structural bioinformatics insights into the CARD‐CARD interaction mediated by the mitochondrial antiviral‐signaling protein of black carp

Structural bioinformatics insights into the CARD‐CARD interaction mediated by the mitochondrial antiviral‐signaling protein of black carp

Deciphering the ATP-binding mechanism(s) in NLRP-NACHT 3D models using structural bioinformatics approaches

ATP-Binding and Hydrolysis in Inflammasome Activation

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