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Cells
Published in Raimund J. Ober, E. Sally Ward, Jerry Chao, Quantitative Bioimaging, 2020
Raimund J. Ober, E. Sally Ward, Jerry Chao
Endoplasmic reticulum (ER). The ER is a reticular, highly interconnected mesh of membrane-bound compartments that are present in the cytoplasm. Proteins that are destined for membrane association (rather than soluble, cytosolic proteins) or secretion from the cell are synthesized on ribosomes that are attached to the ER, and the protein is therefore inserted into the ER membrane whilst it is being synthesized. This is called co-translational insertion. FcRn will be taken as an example. FcRn comprises a dimer of an α-chain and β2-microglobulin. The α-chain is synthesized with a so-called signal peptide (also called a leader peptide) at its N-terminus, which directs this protein to be inserted into the ER membrane as a transmembrane protein (Fig. 9.3). As the signal peptide enters the ER, it is cleaved. The synthesis of the FcRn α-chain continues until a hydrophobic sequence (“transmembrane domain”) is made that anchors the protein in the membrane. Protein synthesis continues so that the C-terminus of the protein is outside the ER (i.e., in the cytosol). Proteins with this orientation in the membrane (N-terminus inside the ER, C-terminus outside) are called type I transmembrane proteins. In addition, β2-microglobulin is synthesized and inserted into the ER with a signal peptide. However, this protein does not have a transmembrane domain and is inserted into the ER as a soluble protein that can then associate with the FcRn α-chain.
Gold nanoparticles induce G2/M cell cycle arrest and enhance the expression of E-cadherin in breast cancer cells
Published in Inorganic and Nano-Metal Chemistry, 2020
Shaimaa Abdel-Ghany, Mennatallah Mahfouz, Nada Ashraf, Hussein Sabit, Emre Cevik, Mokhtar El-Zawahri
E-cadherin, encoded by CDH1 gene, is a transmembrane glycoprotein that confer homotypic interactions on the surface of a neighboring cell, a transmembrane domain, and a cytoplasmic domain that binds to members of the catenin protein family to transduce signals to the cell.[20]CDH1 is downregulated in several types of cancers including BC.[21] Because is responsible for metastasis and progression of the disease, restoring its activity is a potential way to control BC.[22] It is not known whether AuNPs can affect CDH1, however, elucidating this association might help to design therapeutic strategies accordingly. On the other hand, targeting other genes that colocalize with familial types-related genes such as BRC2 is a potential way to regulate its action. Partner and localizer of BRCA2 (PALB2) is one of these genes that coexist with BRCA2 in the nucleus.[23]PALB2 was found to be upregulated in BC,[24] hence, treatments that inhibit its expression is useful. Similarly, the association between AuNPs and PALB2 expression was not highlighted. Therefore, the present study aimed at investigating the association between AuNPs exposure of BC cells and the expression profile of CDH1 and PALB2.
Molecular structure investigation towards pharmacodynamic activity and QSAR analysis on hypoxanthine using experimental and computational tools
Published in Egyptian Journal of Basic and Applied Sciences, 2018
G. Susithra, S. Ramalingam, S. Periandy, R. Aarthi
The heavy atom count of the aromatic molecule is usually making dynamic chemical potential. Accordingly, the heavy atom count was found to be 10 which is very high and molecule was having potential energy for producing consistent drug activity. The GPCR is G protein–coupled receptors (GPCRs) which also known as seven-transmembrane domain receptors and was found to be 0.80 for the present case. Here, the value showed the good signal transduction. The Ion channel modulator value was determined as 0.64 which is enough to modulate the Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. The kinase inhibitor of present case was 0.58 which was enough to modulate its function of protein kinases. The nuclear receptors are multifunctional protein which play key roles in both embryonic development and adult homeostasis which was found to be 3.56 and it was able to transduce signals of their cognate ligands. The Protase inhibitor is an antiviral character of the compound and here the same was found to be 1.97 and it was showed that, the present compound will be acting as antiviral drug.
Ethanol-induced conformational fluctuations of NMDA receptors
Published in Molecular Physics, 2019
Hamid R. Noori, Christian Mücksch, Herbert M. Urbassek
Alcohol intake induces a multi-scale spectrum of spatiotemporal effects, the underlying neurobiology and physiology of which are not yet completely understood. Among a variety of proteins as primary sites of action of ethanol in the central nervous system, the ionotropic glutamatergic N-methyl-d-aspartate (NMDA) receptor represents the most prominent target [1–4]. At concentrations of 5–50 mM that also produce intoxication, ethanol has been shown to inhibit the NMDA-activated ion current in a non-competitive manner [5–10] but also the NMDA-induced calcium influx, long-term potentiation and transmitter release [11–14]. The NMDA receptor is a ligand- and voltage-gated ion channel that is in general an assembly of GluN1, GluN2 (A–D) and GluN3 subunits forming heterodimers with the two-fold symmetry axis running through the entire molecule composed of an amino terminal domain (ATD), a ligand-binding domain (LBD) and a transmembrane domain (TMD). The ion channel activates upon concurrent binding of glycine or d-serine and glutamate at the LBDs of GluN1 and GluN2 subunits, respectively [15] and relief of magnesium blockade of the channel pore by membrane depolarisation. A number of studies have focused on the identification of the molecular locus of alcohol action on NMDA receptors, particularly within the membrane-associated (M) domains of GluN1 and GluN2 subunits. Thereby, substitutions of phenylalanine (F637 and F639) at M3 of GluN1 subunit [16–18] as well as tyrosine T822, methionine M823 and alanine A825 of the GluN2 subunit [19,20] have been shown to influence the sensitivity of NMDA receptor to ethanol. Due to the high conservation level of the M-domains between GluN1 and GluN2 subunits, it is safe to assume that these sites correspond to ethanol sensitive amino acids in the other subunit. Despite the value of these investigations, their search strategies have been hypothesis-driven and site directed as a precise description of the complete structure of NMDA receptor including the M-domains was not available until recently [21,22]. Furthermore, the relationship between the ethanol interaction and the conformational dynamics of the receptor [23,24] is still missing.