scholarly journals STRA6 (vitamin A receptor), as a Novel binding receptor of COVID-19

2021 ◽  
Author(s):  
Mahmoud Elkazzaz ◽  
Amr Kamel Khalil Ahmed ◽  
Israa Mohamed Shamkh ◽  
Mohammed.F. Abo El Magd
Keyword(s):  
Critical Role ◽  
Retinol Binding Protein ◽  
Cell Surface Receptor ◽  
Cytokine Signaling ◽  
Docking Analysis ◽  
Global Pandemic ◽  
Surface Receptor ◽  
A Cell ◽  
Uncertain Etiology ◽  
Entry Receptor

A global pandemic of pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, at the end of 2019. Although, the ACE2 receptor has been shown to be the main entry receptor of COVID-19, but here, in our docking analysis , we predicted and discovered a novel receptor called STRA6 that may play a critical role in the pathogenicity of COVID-19 and explain the common pre and post COVID-19 symptoms with uncertain etiology. STRA6 receptor expressed in many organs and immune cells, upregulated by retinoic acid jm6 (STRA6) was the first protein to be identified in a novel category of proteins, cytokine signaling transporters, due to its ability to function as both a cell surface receptor and a membrane protein that binds to retinol binding protein facilitating cellular uptake of retinol. In agreement to our findings, the main ligand of STRA6 (vitamin/retinol) was found to be significantly reduced during COVID-19 infection.

The transfer of transthyretin and receptor-binding properties from the plasma retinol-binding protein to the epididymal retinoic acid-binding protein

2002 ◽  
Vol 362 (2) ◽  
pp. 265-271 ◽  
Author(s):  
Manickavasagam SUNDARAM ◽  
Daan M. F. van AALTEN ◽  
John B. C. FINDLAY ◽  
Asipu SIVAPRASADARAO
Keyword(s):  
Retinoic Acid ◽  
Binding Protein ◽  
Binding Pocket ◽  
Retinol Binding Protein ◽  
Cell Surface Receptor ◽  
Acid Binding Protein ◽  
The Family ◽  
Surface Receptor ◽  
A Cell ◽  
Plasma Retinol

Members of the lipocalin superfamily share a common structural fold, but differ from each other with respect to the molecules with which they interact. They all contain eight β-strands (A—H) that fold to form a well-defined β-barrel, which harbours a binding pocket for hydrophobic ligands. These strands are connected by loops that vary in size and structure and make up the closed and open ends of the pocket. In addition to binding ligands, some members of the family interact with other macromolecules, the specificity of which is thought to be associated with the variable loop regions. Here, we have investigated whether the macromolecular-recognition properties can be transferred from one member of the family to another. For this, we chose the prototypical lipocalin, the plasma retinol-binding protein (RBP) and its close structural homologue the epididymal retinoic acid-binding protein (ERABP). RBP exhibits three molecular-recognition properties: it binds to retinol, to transthyretin (TTR) and to a cell-surface receptor. ERABP binds retinoic acid, but whether it interacts with other macromolecules is not known. Here, we show that ERABP does not bind to TTR and the RBP receptor, but when the loops of RBP near the open end of the pocket (L-1, L-2 and L-3, connecting β-strands A—B, C—D and E—F, respectively) were substituted into the corresponding regions of ERABP, the resulting chimaera acquired the ability to bind TTR and the receptor. L-2 and L-3 were found to be the major determinants of the receptor- and TTR-binding specificities respectively. Thus we demonstrate that lipocalins serve as excellent scaffolds for engineering novel biological functions.

Vitamin D

1999 ◽  
Vol 277 (2) ◽  
pp. F157-F175 ◽  
Author(s):  
Alex J. Brown ◽  
Adriana Dusso ◽  
Eduardo Slatopolsky
Keyword(s):  
Vitamin D ◽  
Target Genes ◽  
Critical Role ◽  
Active Form ◽  
Cell Surface Receptor ◽  
Dihydroxyvitamin D ◽  
Surface Receptor ◽  
A Cell ◽  
Second Messenger Pathways

The vitamin D endocrine systems plays a critical role in calcium and phosphate homeostasis. The active form of vitamin D, 1,25-dihydroxyvitamin D3[1,25(OH)2D3], binds with high affinity to a specific cellular receptor that acts as a ligand-activated transcription factor. The activated vitamin D receptor (VDR) dimerizes with another nuclear receptor, the retinoid X receptor (RXR), and the heterodimer binds to specific DNA motifs (vitamin D response elements, VDREs) in the promoter region of target genes. This heterodimer recruits nuclear coactivators and components of the transcriptional preinitiation complex to alter the rate of gene transcription. 1,25(OH)2D3also binds to a cell-surface receptor that mediates the activation of second messenger pathways, some of which may modulate the activity of the VDR. Recent studies with VDR-ablated mice confirm that the most critical role of 1,25(OH)2D3is the activation of genes that control intestinal calcium transport. However, 1,25(OH)2D3can control the expression of many genes involved in a plethora of biological actions. Many of these nonclassic responses have suggested a number of therapeutic applications for 1,25(OH)2D3and its analogs.

scholarly journals A high-throughput screen for TMPRSS2 expression identifies FDA-approved compounds that can limit SARS-CoV-2 entry

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yanwen Chen ◽  
Travis B. Lear ◽  
John W. Evankovich ◽  
Mads B. Larsen ◽  
Bo Lin ◽  
...  
Keyword(s):  
Rational Design ◽  
Surface Expression ◽  
In Vitro Models ◽  
Lung Epithelial Cells ◽  
Cell Surface Receptor ◽  
Pharmacokinetic Data ◽  
Drug Induced ◽  
Global Pandemic ◽  
Surface Receptor

AbstractSARS-CoV-2 (2019-nCoV) is the pathogenic coronavirus responsible for the global pandemic of COVID-19 disease. The Spike (S) protein of SARS-CoV-2 attaches to host lung epithelial cells through the cell surface receptor ACE2, a process dependent on host proteases including TMPRSS2. Here, we identify small molecules that reduce surface expression of TMPRSS2 using a library of 2,560 FDA-approved or current clinical trial compounds. We identify homoharringtonine and halofuginone as the most attractive agents, reducing endogenous TMPRSS2 expression at sub-micromolar concentrations. These effects appear to be mediated by a drug-induced alteration in TMPRSS2 protein stability. We further demonstrate that halofuginone modulates TMPRSS2 levels through proteasomal-mediated degradation that involves the E3 ubiquitin ligase component DDB1- and CUL4-associated factor 1 (DCAF1). Finally, cells exposed to homoharringtonine and halofuginone, at concentrations of drug known to be achievable in human plasma, demonstrate marked resistance to SARS-CoV-2 infection in both live and pseudoviral in vitro models. Given the safety and pharmacokinetic data already available for the compounds identified in our screen, these results should help expedite the rational design of human clinical trials designed to combat active COVID-19 infection.

scholarly journals Correlated STORM-homoFRET Imaging: Applications to the Study of Membrane Receptor Self-Association and Clustering

2021 ◽  
Author(s):  
Amine Driouchi ◽  
Scott Gray-Owen ◽  
Christopher M Yip
Keyword(s):  
Spatial Distribution ◽  
Membrane Proteins ◽  
Complex Mixture ◽  
Cell Surface Receptor ◽  
Oligomeric State ◽  
Imaging Approach ◽  
Surface Receptor ◽  
A Cell ◽  
Self Association ◽  
And Function

Mapping the self-organization and spatial distribution of membrane proteins is key to understanding their function. We report here on a correlated STORM/homoFRET imaging approach for resolving the nanoscale distribution and oligomeric state of membrane proteins. Live cell homoFRET imaging of CEACAM1, a cell-surface receptor known to exist in a complex equilibrium between monomer and dimer/oligomer states, revealed highly heterogenous diffraction-limited structures on the surface of HeLa cells. Correlated super-resolved STORM imaging revealed that these structures comprised a complex mixture and spatial distribution of self-associated CEACAM1 molecules. This correlated approach provides a compelling strategy for addressing challenging questions about the interplay between membrane protein concentration, distribution, interaction, clustering, and function.

P4-054: KLOTHO ENHANCES NEURONAL ACTIVITY THROUGH INTERACTION WITH A CELL-SURFACE RECEPTOR

2006 ◽  
Vol 14 (7S_Part_27) ◽  
pp. P1453-P1454
Author(s):  
Nicola J. Corbett ◽  
Kate Fisher ◽  
Helen A. Rowland ◽  
Alys C. Jones ◽  
Nigel M. Hooper
Keyword(s):  
Cell Surface ◽  
Neuronal Activity ◽  
Cell Surface Receptor ◽  
Surface Receptor ◽  
A Cell

scholarly journals gp96 Is a Human Colonocyte Plasma Membrane Binding Protein for Clostridium difficile Toxin A

2008 ◽  
Vol 76 (7) ◽  
pp. 2862-2871 ◽  
Author(s):  
Xi Na ◽  
Ho Kim ◽  
Mary P. Moyer ◽  
Charalabos Pothoulakis ◽  
J. Thomas LaMont
Keyword(s):  
Plasma Membrane ◽  
Clostridium Difficile ◽  
Binding Protein ◽  
Membrane Binding ◽  
Cell Surface Receptor ◽  
Toxin A ◽  
Surface Receptor ◽  
A Cell ◽  
Plasma Membrane Binding

ABSTRACT Clostridium difficile toxin A (TxA), a key mediator of antibiotic-associated colitis, requires binding to a cell surface receptor prior to internalization. Our aim was to identify novel plasma membrane TxA binding proteins on human colonocytes. TxA was coupled with biotin and cross-linked to the surface of HT29 human colonic epithelial cells. The main colonocyte binding protein for TxA was identified as glycoprotein 96 (gp96) by coimmunoprecipitation and mass spectrum analysis. gp96 is a member of the heat shock protein family, which is expressed on human colonocyte apical membranes as well as in the cytoplasm. TxA binding to gp96 was confirmed by fluorescence immunostaining and in vitro coimmunoprecipitation. Following TxA binding, the TxA-gp96 complex was translocated from the cell membrane to the cytoplasm. Pretreatment with gp96 antibody decreased TxA binding to colonocytes and inhibited TxA-induced cell rounding. Small interfering RNA directed against gp96 reduced gp96 expression and cytotoxicity in colonocytes. TxA-induced inflammatory signaling via p38 and apoptosis as measured by activation of BAK (Bcl-2 homologous antagonist/killer) and DNA fragmentation were decreased in gp96-deficient B cells. We conclude that human colonocyte gp96 serves as a plasma membrane binding protein that enhances cellular entry of TxA, participates in cellular signaling events in the inflammatory cascade, and facilitates cytotoxicity.

230. Megalin, RAP and Nkx3.1 expression in the developing reproductive tract of a marsupial, the tammar wallaby

2008 ◽  
Vol 20 (9) ◽  
pp. 30
Author(s):  
M. Gamat ◽  
M. B. Renfree ◽  
A. J. Pask ◽  
G. Shaw
Keyword(s):  
Cell Surface ◽  
Reproductive Tract ◽  
Tammar Wallaby ◽  
Cell Surface Receptor ◽  
Urogenital Sinus ◽  
Receptor Associated Protein ◽  
Wide Range ◽  
Surface Receptor ◽  
A Cell ◽  
Strong Staining

Androgens induce the differentiation of the urogenital sinus (UGS) to form a prostate. An early marker of this response is upregulation of the transcription factor Nkx3.1 in the urogenital epithelium in the precursors of prostatic buds. In tammars, prostate differentiation begins ~3 weeks after birth and after the time the testis starts to secrete androgens, and 2 weeks after androgen stimulated Wolffian duct differentiation. The reason for this delay in prostate differentiation is unexplained. Androgen receptors are present in the UGS, and the potent androgen, androstanediol, induces prostatic development in females. Whilst androgens may diffuse into cells by across the cell membrane, there is increasing evidence that steroids are also internalised actively via the cell-surface transport molecule Megalin. We are exploring the possibility that the delay may be related to the establishment of a Megalin-mediated pathway. Megalin is a cell surface receptor expressed on epithelia and mediates the endocytosis of a wide range of ligands, including SHBG-bound sex steroids. Megalin action is regulated by Receptor Associated Protein (RAP), which acts as an antagonist to Megalin action. This study cloned partial sequences of Megalin, RAP and Nkx3.1 and examined their expression in the developing urogenital sinus of the tammar wallaby using RT–PCR. The cellular distribution of Megalin protein in the developing UGS was examined using immunohistochemistry. Megalin, RAP and Nkx3.1 in the tammar were all highly conserved with eutherian orthologueues. Megalin and Nkx3.1 transcripts were detected in the liver, kidney, ovary, testis and developing urogenital sinus of male and female tammars. In the developing UGS of the tammar, there was strong staining for Megalin protein in the urogenital epithelium with some diffuse staining in the surrounding mesenchyme. Together, these results suggest that Megalin could be a key gene in the mediation of androgen action in prostatic development in the tammar wallaby.

Sign in / Sign up

Export Citation Format

Share Document