T1 - Synthesis of platelet-activating factor by endothelial cells

Understanding ribosomes is important not only because of their crucial role as the protein factories of all living cells, but also because many antibiotics work by targeting bacterial ribosomes. Research on ribosomes by Noller and others has led to the development of novel antibiotics that hold promise for use against drug-resistant bacteria.

We can regard protein synthesis as a chemical reaction, ..

Overview of protein synthesis; Protein processing;

The role of G factor in protein synthesis

AB - Insulin rapidly stimulates protein synthesis in a wide variety of tissues. This stimulation is associated with phosphorylation of several translational initiation and elongation factors, but little is known about the signaling pathways leading to these events. To study these pathways, we have used a myeloid progenitor cell line (32D) which is dependent on interleukin 3 but insensitive to insulin because of the very low levels of insulin receptor (IR) and the complete lack of insulin receptor substrate (IRS)-signaling proteins (IRS-1 and IRS-2). Expression of more IR permits partial stimulation of mitogen-activated protein kinase by insulin, and expression of IRS-1 alone mediates insulin stimulation of the 70-kDa S6 kinase (pp70S6K) by the endogenous IR. However, expression of both IR and IRS-1 is required for stimulation of protein synthesis. Moreover, this effect requires activation of phosphatidylinositol 3-kinase (PI3K), as determined by wortmannin inhibition and the use of an IRS-1 variant lacking all Tyr residues except those which activate PI3K. Stimulation of general protein synthesis does not involve activation by IRS-1 of GRB-2-SOS-p21ras or SH-PTP2, since IRS-1 variants lacking the SH2-binding Tyr residues for these proteins are fully active. Nor does it involve pp70S6K, since rapamycin, while strongly inhibiting the synthesis of a small subset of growth-regulated proteins, only slightly inhibits total protein synthesis. Recruitment of mRNAs to the ribosome is enhanced by phosphorylation of eIF4E, the cap-binding protein, and PHAS-I, a protein that specifically binds eIF4E. The behavior of cell lines containing IRS-1 variants and inhibition by wortmannin and rapamycin indicate that the phosphorylation of both proteins requires IRS-1-mediated stimulation of PI3K and pp70S6K but not mitogen-activated protein kinase or SH-PTP2.

Protein synthesis was in the spotlight this past year, ..

When the crystal structure of EF-G:GDP was solved, it revealed a surprising and elegant structural feature. Elongation factor G consists of five structural domains, and from sequence comparisons Domains 1 and 2 were expected to be similar in conformation to EF-Tu Domains 1 and 2. This conformational "mimic" does indeed occur. Domains 3 and 5 of EF-G contain protein folds similar to some ribosomal proteins whose structures are known, while Domain 4 adopts an unusual fold. This domain is elongated and points away from the rest of the protein.

T1 - Organization of the genes for protein synthesis elongation factors Tu and G in the cyanobacterium Anacystis nidulans
The protein synthesis initiation factor 2 G-domain. …

The protein synthesis initiation factor 2 G-domain

The structure and function of the ribosome are fascinatinglycomplex. Two-thirds of the ribosome consist of ribosomal RNA (rRNA),while over 50 ribosomal proteins make up the rest. The geneticinformation is delivered to the ribosome by a messenger RNA(mRNA). Transfer RNAs (tRNAs) are adapter molecules, each equipped withan anticodon to match the codons in the mRNA, and charged with an aminoacid that corresponds to the anticodon as dictated by the geneticcode. The ribosome contains three tRNA-binding sites: A, P, and E (seeelongation cycle box, or watch a ). In addition to mRNA and tRNAs, the ribosomeinteracts with protein factors such as the elongation factors Tu (EF-Tu)and G (EF-G), that are important players in the so-called elongationcycle. The elongation cycle results in the addition of an amino acid tothe nascent peptide chain, and consists of three main steps. In thedecoding step, a ternary complex comprised of an aminoacyl-tRNA(aa-tRNA), EF-Tu, and GTP binds to the ribosome,leading to the recognition of the codon by the anticodon. The followingstep is the peptidyl transfer. Here the peptide chain bound to theP-site tRNA is covalently linked to the amino acid bound to the A-sitetRNA. In the translocation step, the position of the mRNA/tRNA complexshifts by one codon, accompanied by a ratchet-like motion of theribosomal subunits.

More recently the regulation of protein synthesis and translation factors ..

Organization of the genes for protein synthesis …

Some other studies performed in systems by Zhang () demonstrated that human TRAP1 is ableto rescue phenotypes in PINK1 loss-of-function flies, but has onlyminor effects on phenotypes of flies deficient of PARKIN, anotherprotein associated with autosomal recessive, early-onset PD. Inaddition, detrimental effects observed after RNAi-mediatedsilencing of complex I subunits were rescued by TRAP1 in. Remarkably, these studies confirm the metaboliccontrol by TRAP1, albeit in different experimental systems: infact, the lack of functional mitochondria obviously coincides withreduced levels of complex I subunits, impaired complex I activityand a decline in ATP content. TRAP1 protective effects require itsATP binding properties, as ATP-binding deficient TRAP1 mutants wereunable to rescue this activity. Considering that functional ETCcauses polarization of the mitochondrial membrane and thatdepolarization of mitochondria is required to initiate mitophagy,it can be speculated that TRAP1 might negatively regulate mitophagyby maintaining the ETC in a functional state ().

06/01/2018 · Protein synthesis regulation by leucine

and eukaryotic initiation factor 4E binding protein 1 ..

The structural basis for TnaC-mediated translational stalling wasaddressed by obtaining a 5.8-Å cryo-EM map of the ribosome stalled byTnaC and high concentrations of tryptophan (Fig. 8). The cryo-EM datashows that the nascent chain adopts a distinct conformation in the exittunnel. We applied MDFF to obtain an atomic model of the entire ribosomeand the stalling nascent chain (Fig. 8F). The model allowed us to mapthe contacts between TnaC and the exit tunnel, as well as proposepossible communication pathways that would lead to inactivation of thecatalytic center of the ribosome (the so-called peptidyltransferasecenter, or PTC). One of the main findings was that two criticalribosomal residues at the PTC adopt conformations that are incompatiblewith cohabitation by release factors, which catalyze termination ofprotein synthesis.