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TLR4 binds NAMPT. 36 / 37
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"Moreover, recent studies have shown that visfatin could bind and activate the Toll-like receptor 4 (95) and also due to its insulin-mimetic activity, can bind the insulin receptor and cause insulin resistance and consequently regulate glucose levels (96)."
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"Indeed, in silico analysis predicted high‐affinity binding between NAMPT and TLR4 (Figure 4k)."
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"To further gain insights into NAMPT–TLR4 interaction we performed molecular docking between TLR4 homodimer and NAMPT homodimer."
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"Furthermore, the in vitro interaction between NAMPT and TLR4 or CYBB, as evaluated by a fluorescence binding experiment with recombinant proteins and fluorescently labeled TLR4 or CYBB with NAMPT, revealed a sufficiently high affinity (TLR4, 219 nM; CYBB, 896nM) (Figure 1)."
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"Using an integrated approach combining bioinformatics and functional and structural analyses, we investigated the interaction between NAMPT and TLR4 at the molecular level."
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"To identify the domain required for the interaction between NAMPT and TLR4, we employed constructs tagged with GST or Myc–NAMPT and Flag–TLR4."
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"Treatment with TAT–NAMPT (aa 40–69) diminished the binding of NAMPT to TLR4, indicating that this region binds TLR4 (Figure 3B left)."
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"Our analysis of the structure of the MD-2 and LPS complex, however, indicates that LPS binding to TLR4 maps to the protruding region of NAMPT and PBEF (S402-N412), suggesting that NAMPT and PBEF may intrinsically adopt a conformation capable of direct TLR4 binding and activation."
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"Furthermore, the extracellular binding of NAMPT to toll like receptor 4 (TLR4) results in NF-kappaB phosphorylation and activation, providing information on protein functionality [XREF_BIBR]."
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"These findings show that NAMPT aa 57–65 and aa 52–56 are necessary for interacting with TLR4 or CYBB, respectively, demonstrating that NAMPT interactions with TLR4 and CYBB are genetically separate."
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"The minimized model for the NAMPT–TLR4 complex ( xref ) confirms the role of the NAMPT-positive patches, showing the presence of stabilizing electrostatic interactions between Lys residues 48, 68, 71, 73 and TLR4 negatively charged carboxylic moieties ( xref )."
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"Molecular docking studies on a minimized model of the NAMPT–TLR4 complex reveal a role for NAMPT-positive patches and the presence of stabilizing electrostatic interactions between K48, K68, K71, K73 with the negatively charged carboxyl moieties of TLR4 [40]."
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"Finally, the involvement of the two loops in receptor binding was supported by NAMPT-TLR4 docking simulations."
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"Here, we have analyzed the kinetics of the NAMPT–TLR4 complex formation by assessing the direct binding of NAMPT to immobilized TLR4."
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"To shed light on the molecular NAMPT–TLR4 interaction, we started from the evidence that bacterial NAMPT does not act as a cytokine ( xref )."
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"Recent studies have shown that visfatin directly binds to TLR4. xref , xref Thus, we examined the involvement of TLR4 in the induction of cellular senescence by visfatin in hDPCs."
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"eNAMPT stimulates the NOX-mediated redox regulatory pathway, and NAMPT associates with TLR4 [11,17,18], possibly leading to upregulation of NLRP3 and pro-IL1β expression via the NF-κB signaling pathway (Figure 1A)."
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"The extracellular form of NAMPT (eNAMPT) binds TLR4, triggering an inflammatory response and so acting as a damage-induced molecular marker."
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"Intriguingly, NAMPT can orchestrate chronic inflammatory responses by binding with Toll-Like Receptor 4 (TLR4) and C–C chemokine receptor type 5 (CCR5) ( Nencioni et al., 2014 )."
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"eNAMPT stimulates the NOX-mediated redox regulatory pathway, and NAMPT associates with TLR4 [ xref , xref , xref ], possibly leading to upregulation of NLRP3 and pro-IL1β expression via the NF-κB signaling pathway ( xref A)."
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"To identify the domain required for the interaction between NAMPT and TLR4, we employed constructs tagged with GST or Myc–NAMPT and Flag–TLR4."
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"In 293T cells, the N-terminus of NAMPT bound TLR4 and the extracellular leucine-rich region (LRR domain) of TLR4 were essential for the interaction with NAMPT ( xref A)."
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"Moreover, recent studies have shown that visfatin could bind and activate the Toll-like receptor 4 ( xref ) and also due to its insulin-mimetic activity, can bind the insulin receptor and cause insulin resistance and consequently regulate glucose levels ( xref )."
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"This is in keeping with both the SPR results, showing that the protein strongly binds to the receptor in the absence of MD2, and the docking results, revealing that NAMPT interacts with TLR4 in its concave surface, similarly to MD2 ( xref )."
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"Treatment with TAT–NAMPT (aa 40–69) diminished the binding of NAMPT to TLR4, indicating that this region binds TLR4 ( xref B left)."
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"To determine the minimum aa sequence necessary for NAMPT–TLR4 binding, we utilized the PredictProtein software (; accessed on 9 July 2022), which predicts elements of protein function and structure using database searches, homology-based inference, machine learning, and artificial intelligence. [ xref ]."
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"NAMPT binds TLR4 in a concentration-dependent manner, with an equilibrium dissociation constant (K D ) of about 18 nM ( xref and xref )."
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"Extracellular NAMPT mainly binds to its receptors TLR4 to activate downstream signalling pathway ( Camp et al., 2015 ), including NF-κB, MAPK, STAT3 ( Kim et al., 2008 )."
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"PredictProtein predicted that aa 57–65 of NAMPT were required for binding TLR4, consistent with findings that NAMPT–TLR4 binding in 293T cells was diminished by TAT–NAMPT (aa 57–65) in a concentration-dependent manner ( xref B right)."
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"We showed here that PDGF promoted NF-κB phosphorylation through extracellular NAMPT binding to TLR4 on PASMCs surface, and prior inhibition of TLR4 with TAK-242 or pre-suppression of NF-κB with PDTC i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Furthermore, the extracellular binding of NAMPT to toll-like receptor 4 (TLR4) results in NF-κB phosphorylation and activation, providing information on protein functionality [ xref ]."
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"These findings suggest that rCT-NAMPT has a therapeutic effect against DSS-induced colitis through inhibiting the NAMPT–TLR4 or –CYBB interaction in vivo."
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"Molecular docking studies on NAMPT–TLR4 interaction."
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"Molecular docking studies on a minimized model of the NAMPT–TLR4 complex reveal a role for NAMPT-positive patches and the presence of stabilizing electrostatic interactions between K48, K68, K71, K73 with the negatively charged carboxyl moieties of TLR4 [ xref ]."
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"Our group recently confirmed the binding of eNAMPT to TLR4 in macrophage cellular model ( xref ), performing surface plasmon resonance (SPR) under the same conditions previously established for the NAMPT-TLR4 interaction ( xref )."
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"It has been shown that visfatin can bind to the insulin receptor [114,120] or TLR4 [121]."
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