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Translation
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
After the Thr59Ser and Thr45Ala substitutions, Lago et al. (1998) also studied single Glu76Asp and Pro78Asn mutants by in vivo and in vitro functional assays. Therefore, the substitutions were inserted at amino acid residues which either interacted with the operator RNA or were involved in stabilizing the conformation of the FG loop, the site of the major quasi-equivalent conformational change (for more detail, see Chapter 21). The results with the variant RNA operators revealed the robustness of the operator-coat protein interaction and the requirement for both halves of a protein dimer to contact RNA in order to achieve tight binding. It was suggested that there might be a direct link between the conformation of the FG loop and RNA binding. This point was strengthened by the recent finding of Stockley's team that the Pro78 from the FG loop was essential for viral infectivity (Hill et al. 1997).
Zika: An Ancient Virus Incipient into New Spaces
Published in Jagriti Narang, Manika Khanuja, Small Bite, Big Threat, 2020
Bennet Angel, Neelam Yadav, Jagriti Narang, Surender Singh Yadav, Annette Angel, Vinod Joshi
Immature virions present in the cytoplasm contain a lipid membrane having prM, and envelope proteins are present on the surface in icosahedral fashion (Kostyuchenko et al., 2016). Trimers of prM-envelope protein heterodimers are formed for the translation and processing of viral polyproteins. prM translocation is assisted by C protein, which contains a site for RNA interaction and shows interaction due to C-terminal trans-domain and also serves as signal sequence. Immature virions become mature when they move around the low-pH environment of trans-Golgi network (Dai et al., 2016). In the low-pH environment, prM can be cleaved by host protease. There is change in the conformation of E protein dimer, and the remaining portion is still associated with the virions (Barba-Spaeth et al., 2016). Upon increase in pH, the mature virion separates from the pr peptide as the virion is exported from the cell using host secretory machinery. The mature ZIKV envelope protein has only one glycosylation at Asnl54, which makes it differ from the dengue virus envelope protein, which is glycosylated at two sites (Asnl53 and Asn57) (Haddow et al., 2012). The molecular pattern present on infected cells can be easily recognized by pattern recognition receptors (RIG-1/MDA5 and TLR3) induced by the innate immune response. It ultimately leads to the production of interferons (IFN-I and IFN-III) (Faye et al., 2014). Transmembrane IFN inducible proteins are expressed, which inhibit the replication of ZIKV. IFITM3 and IFITM1 have also been shown to inhibit the replication of ZIKV (Barba-Spaeth et al., 2016; Dai et al., 2016; Kostyuchenko et al., 2016; Sirohi et al., 2016) (Figs. 6.5 and 6.6).
GDF15: a potential therapeutic target for type 1 diabetes
Published in Expert Opinion on Therapeutic Targets, 2022
Soumyadeep Sarkar, John T. Melchior, Hayden R. Henry, Farooq Syed, Raghavendra G. Mirmira, Ernesto S. Nakayasu, Thomas O. Metz
GDF15 is a secreted cytokine, independently discovered by three research groups in 1997 [14–16]. Despite its low sequence homology to TGF-β, GDF15 has been classified as a distant member of the TGF-β family due to the presence of a unique cysteine knot characteristic of this class of molecules. GDF15 is expressed in most tissues as a 308 amino acid propeptide monomer form, which dimerizes via a disulfide linkage between the cysteines in the C-terminus. The pro-protein dimer undergoes proteolytic cleavage at an RXXR residue by a furine-like protease to release the mature GDF15 dimer of 25 kDa into the extracellular space [15,17–21]. In plasma, GDF15 exists in a broad concentration ranging from 0.15 to 1.15 ng/mL and potentially in both pro-GDF15 and mature GDF15 forms [21,22]. Levels of GDF15 are impacted by a plethora of metabolic factors, exercise, tissue injury, pregnancy, hypoxia, and drugs like metformin and rapamycin represented in Figure 2. Given its central role and metabolic sensitivity, GDF15 is emerging as a premier biomarker to determine prognoses in a number of health disorders, including T1D [11,23,24].
Physicochemical properties and oxygen affinity of glutaraldehyde polymerized crocodile hemoglobin: the new alternative hemoglobin source for hemoglobin-based oxygen carriers
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Napaporn Roamcharern, Wisarut Payoungkiattikun, Preeyanan Anwised, Bancha Mahong, Nisachon Jangpromma, Sakda Daduang, Sompong Klaynongsruang
The Poly-Hbs possessed various heterogeneous molecular weight distributions on SDS gels (Figure 1). The heterogeneous molecular weight distributions also increased depending on the increase of the GTA concentrations in a dose-dependent manner. Native-cHb revealed double bands of Hb monomer at 15 and 16 kDa, which corresponds to α and β subunits, respectively [29]. The protein band of 29 kDa was also observed as an Hb dimer and may be carbonic anhydrase [30]. However, Poly-cHbs revealed the heterogeneous molecular weight products of protein dimer (29–30 kDa), trimer and tetramer (45–75 kDa), and diffused banding patterns (>75 kDa) (Figure 1(A) and Figure 1(B)). In contrast, a slight decrease in the intensity of the α subunit band was observed along with an increase of the GTA concentration. In contrast, the Native-hHb revealed the single band of an Hb monomer at 13–15 kDa (α and β subunit). The Hb dimer was observed at 31 kDa and the other unidentified bands were observed at 24 and 60 kDa. It is important to note that Poly-hHb patterns were similar to Poly-cHb patterns, which exhibited heterogeneous molecular weight products (Figure 1(C) and Figure 1(D)). However, a large number of precipitates were observed in Poly-Hb samples derived from the GTA concentration ranging from 0.175–0.300% (v/v). Thus, only Poly-Hb samples in the GTA concentration range of 0.025–0.150% (v/v) were properly selected for further experiments.
ZBTB20 promotes cell migration and invasion of gastric cancer by inhibiting IκBα to induce NF-κB activation
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Yangmei Zhang, Xichang Zhou, ManMan Zhang, Long Cheng, Youwei Zhang, Xiang Wang
In cancer, NF-κB is proposed to contribute to oncogenesis through the induction of genes encoding proteins involved in promoting invasion and migration and suppressing apoptosis. Suppression of NF-κB activity through the inhibition of IκBα degradation contributes to the decreased cell migration in triple negative breast cancer [19]. Activating the NF-κB signaling pathway also promoted cell invasion, migration and proliferation in gastric cancer [20]. The NF-κB protein dimer is complexed with IκB protein under resting conditions. After stimulation with cytokines or lipopolysaccharide, IκBα is phosphorylated by upstream IKK (IκB kinases) and degradation, finally resulting in the activation of NF-κB [21]. Consistently, our loss- and gain- of-function studies showed that ZBTB20 knockdown significantly induced IκBα expression, and then resulted in the decrease in phosphorylation of NF-κBp65 in gastric cancer cell lines. Consistent with our findings, and mechanistically, ZBTB20 promotes NF-κB activation through inhibiting IκBα gene transcription and governing IκBα protein expression [12]. Moreover, ZBTB20 promotes hepatocyte proliferation and activation of NF-κB in regenerating liver after partial hepatectomy [13].