In Silico Modeling of Human α2C-Adrenoreceptor Interaction with Filamin-2

Pawłowski, Marcin; Saraswathi, Saras; Motawea, Hanaa K. B.; Chotani, Maqsood A.; Kloczkowski, Andrzej

doi:10.1371/journal.pone.0103099

Cited by 13 publications

(14 citation statements)

References 57 publications

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“…This intimate association appears to be mediated by a direct interaction between α 2C -ARs and filamin-2, a cross-linker of actin filaments (Motawea et al, 2013). Indeed, further in silico protein-protein docking examinations confirmed that the interaction between α 2C -AR and F-actin occurs via the direct binding of α 2C -AR to filamin, the actin binding protein (Pawlowski et al, 2014). Interestingly, this interaction has evolved only in warm blooded animals (Pawlowski et al, 2014).…”

Section: Rp and The Actin Cytoskeletonmentioning

confidence: 92%

“…Indeed, further in silico protein-protein docking examinations confirmed that the interaction between α 2C -AR and F-actin occurs via the direct binding of α 2C -AR to filamin, the actin binding protein (Pawlowski et al, 2014). Interestingly, this interaction has evolved only in warm blooded animals (Pawlowski et al, 2014). Therefore, elucidation of similar protein-protein interactions can help establish more efficient therapies for exaggerated vasoconstriction.…”

Section: Rp and The Actin Cytoskeletonmentioning

confidence: 92%

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Raynaud’s Phenomenon: A Brief Review of the Underlying Mechanisms

et al. 2016

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Raynaud’s phenomenon (RP) is characterized by exaggerated cold-induced vasoconstriction. This augmented vasoconstriction occurs by virtue of a reflex response to cooling via the sympathetic nervous system as well as by local activation of α2C adrenoceptors (α2C-AR). In a cold-initiated, mitochondrion-mediated mechanism involving reactive oxygen species and the Rho/ROCK pathway, cytoskeletal rearrangement in vascular smooth muscle cells orchestrates the translocation of α2C-AR to the cell membrane, where this receptor readily interacts with its ligand. Different parameters are involved in this spatial and functional rescue of α2C-AR. Of notable relevance is the female hormone, 17β-estradiol, or estrogen. This is consistent with the high prevalence of RP in premenopausal women compared to age-matched males. In addition to dissecting the role of these various players, the contribution of pollution as well as genetic background to the onset and prevalence of RP are also discussed. Different therapeutic approaches employed as treatment modalities for this disease are also highlighted and analyzed. The lack of an appropriate animal model for RP mandates that more efforts be undertaken in order to better understand and eventually treat this disease. Although several lines of treatment are utilized, it is important to note that precaution is often effective in reducing severity or frequency of RP attacks.

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Section: Rp and The Actin Cytoskeletonmentioning

confidence: 92%

Section: Rp and The Actin Cytoskeletonmentioning

confidence: 92%

Raynaud’s Phenomenon: A Brief Review of the Underlying Mechanisms

et al. 2016

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“…Likewise, the structural model of either SmpB or ArfA was generated by submitting the amino acid sequence to the I-TASSER in comparison with SmpB (PDB code: 1k8h) or ArfA (PDB code: 2tmaA), accordingly. The output of I-TASSER was analyzed using Pymol version 1.4.1 (Pawlowski et al, 2014 ). HADDOCK (High Ambiguity Driven protein-protein DOCKing) was executed to dock SmpB and SN, ArfA and PA-2 separately (de Vries et al, 2010 ; van Zundert et al, 2016 ).…”

Section: Methodsmentioning

confidence: 99%

Genetic Selection of Peptide Aptamers That Interact and Inhibit Both Small Protein B and Alternative Ribosome-Rescue Factor A of Aeromonas veronii C4

et al. 2016

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Aeromonas veronii is a pathogenic gram-negative bacterium, which infects a variety of animals and results in mass mortality. The stalled-ribosome rescues are reported to ensure viability and virulence under stress conditions, of which primarily include trans-translation and alternative ribosome-rescue factor A (ArfA) in A. veronii. For identification of specific peptides that interact and inhibit the stalled-ribosome rescues, peptide aptamer library (pTRG-SN-peptides) was constructed using pTRG as vector and Staphylococcus aureus nuclease (SN) as scaffold protein, in which 16 random amino acids were introduced to form an exposed surface loop. In the meantime both Small Protein B (SmpB) which acts as one of the key components in trans-translation, and ArfA were inserted to pBT to constitute pBT-SmpB and pBT-ArfA, respectively. The peptide aptamer PA-2 was selected from pTRG-SN-peptides by bacterial two-hybrid system (B2H) employing pBT-SmpB or pBT-ArfA as baits. The conserved sites G133K134 and D138K139R140 of C-terminal SmpB were identified by interacting with N-terminal SN, and concurrently the residue K62 of ArfA was recognized by interacting with the surface loop of the specific peptide aptamer PA-2. The expression plasmids pN-SN or pN-PA-2, which combined the duplication origin of pRE112 with the neokanamycin promoter expressing SN or PA-2, were created and transformed into A. veronii C4, separately. The engineered A. veronii C4 which endowing SN or PA-2 expression impaired growth capabilities under stress conditions including temperatures, sucrose, glucose, potassium chloride (KCl) and antibiotics, and the stress-related genes rpoS and nhaP were down-regulated significantly by Quantitative Real-time PCR (qRT-PCR) when treating in 2.0% KCl. Thus, the engineered A. veronii C4 conferring PA-2 expression might be potentially attenuated vaccine, and also the peptide aptamer PA-2 could develop as anti-microbial drugs targeted to the ribosome rescued factors in A. veronii.

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“…Further, structures were refined in explicit solvent and clustered according to HADDOCK score. Upon cluster-structural analysis, 10 lowest energy models were selected, and among these, the best one was characterized on the basis of lowest HADDOCK score, electrostatic energy and Z-score [ 38 , 39 ].…”

Section: Methodsmentioning

confidence: 99%

Cross Talk between KGF and KITLG Proteins Implicated with Ovarian Folliculogenesis in Buffalo Bubalus bubalis

et al. 2015

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Molecular interactions between mesenchymal-derived Keratinocyte growth factor (KGF) and Kit ligand (KITLG) are essential for follicular development. These factors are expressed by theca and granulosa cells. We determined full length coding sequence of buffalo KGF and KITLG proteins having 194 and 274 amino acids, respectively. The recombinant KGF and KITLG proteins were solubilized in 10 mM Tris, pH 7.5 and 50 mM Tris, pH 7.4 and purified using Ni-NTA column and GST affinity chromatography, respectively. The purity and molecular weight of His-KGF (~23 kDa) and GST-KITLG (~57 kDa) proteins were confirmed by SDS-PAGE and western blotting. The co-immunoprecipitation assay accompanied with computational analysis demonstrated the interaction between KGF and KITLG proteins. We deduced 3D structures of the candidate proteins and assessed their binding based on protein docking. In the process, KGF specific residues, Lys123, Glu135, Lys140, Lys155 and Trp156 and KITLG specific ones, Ser226, Phe233, Gly234, Ala235, Phe236, Trp238 and Lys239 involved in the formation of KGF-KITLG complex were detected. The hydrophobic interactions surrounding KGF-KITLG complex affirmed their binding affinity and stability to the interacting interface. Additionally, in-silico site directed mutagenesis enabled the assessment of changes that occurred in the binding energies of mutated KGF-KITLG protein complex. Our results demonstrate that in the presence of KITLG, KGF mimics its native binding mode suggesting all the KGF residues are specific to their binding complex. This study provides an insight on the critical amino acid residues participating in buffalo ovarian folliculogenesis.

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In Silico Modeling of Human α2C-Adrenoreceptor Interaction with Filamin-2

Cited by 13 publications

References 57 publications

Raynaud’s Phenomenon: A Brief Review of the Underlying Mechanisms

Raynaud’s Phenomenon: A Brief Review of the Underlying Mechanisms

Genetic Selection of Peptide Aptamers That Interact and Inhibit Both Small Protein B and Alternative Ribosome-Rescue Factor A of Aeromonas veronii C4

Cross Talk between KGF and KITLG Proteins Implicated with Ovarian Folliculogenesis in Buffalo Bubalus bubalis

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