Interactions of the protein tyrosine phosphatase PTPN3 with viral and cellular partners through its PDZ domain: insights into structural determinants and phosphatase activity.

The human protein tyrosine phosphatase non-receptor type 3 (PTPN3) is a phosphatase containing a PDZ (PSD-95/Dlg/ZO-1) domain that has been found to play both tumor-suppressive and tumor-promoting roles in various cancers, despite limited knowledge of its cellular partners and signaling functions. Notably, the high-risk genital human papillomavirus (HPV) types 16 and 18 and the hepatitis B virus (HBV) target the PDZ domain of PTPN3 through PDZ-binding motifs (PBMs) in their E6 and HBc proteins respectively. This study focuses on the interactions between the PTPN3 PDZ domain (PTPN3-PDZ) and PBMs of viral and cellular protein partners.

Regulatory Interplay between RNase III and Antisense RNAs in E. coli: the Case of AsflhD and FlhD, Component of the Master Regulator of Motility.

In order to respond to ever-changing environmental cues, bacteria display resilient regulatory mechanisms controlling gene expression. At the post-transcriptional level, this is achieved by a combination of RNA-binding proteins, such as ribonucleases (RNases), and regulatory RNAs, including antisense RNAs (asRNAs). Bound to their complementary mRNA, asRNAs are primary targets for the double-strand-specific endoribonuclease, RNase III.

Assessment of helicopter passengers' vibration discomfort: proposal for improvement of the ISO 2631-1 standard.

High levels of vibration exist in helicopters and manufacturers are seeking to quantify vibration discomfort. They use the ISO 2631-1 standard, proposed for all types of transport. This study aimed to verify the validity of this index in the specific case of helicopters.

Ectopic third mandibular molar: evaluation of surgical practices and meta-analysis.

Objectives: To identify the preferred surgical approach (intra- or extra-oral) to remove an ectopic third mandibular molar (ETMM) according on its location and presence of an associated cyst or cutaneous fistula, and to determine the indications for a graft or osteosynthesis.

Materials And Methods: A surgical practice questionnaire was distributed to oral and maxillo-facial surgeons attending a National Congress of the French Society of Stomatology, Maxillo-facial and Oral Surgery. A systematic review of the literature and meta-analysis was carried on Pubmed, Cochrane, Embase and ScienceDirect databases using the MeSH terms: "Ectopic teeth", "Third molar", "Mandibular".

Role of PDZ-binding motif from West Nile virus NS5 protein on viral replication.

West Nile virus (WNV) is a Flavivirus, which can cause febrile illness in humans that may progress to encephalitis. Like any other obligate intracellular pathogens, Flaviviruses hijack cellular protein functions as a strategy for sustaining their life cycle. Many cellular proteins display globular domain known as PDZ domain that interacts with PDZ-Binding Motifs (PBM) identified in many viral proteins.

Surgical approach of ectopic maxillary third molar avulsion: Systematic review and meta-analysis.

Ectopic maxillary third molars (EMTM) are extracted mainly by the Caldwell-Luc technique but also by nasal endoscopy. There is currently no consensus on the treatment of this eruption and its management is heterogeneous and multidisciplinary. Two literature searches were performed with no time restrictions via Pubmed.

Quick compensatory mechanisms for tongue posture stabilization during speech production.

The human tongue is atypical as a motor system since its movement is determined by deforming its soft tissues via muscles that are in large part embedded in it (muscular hydrostats). However, the neurophysiological mechanisms enabling fine tongue motor control are not well understood. We investigated sensorimotor control mechanisms of the tongue through a perturbation experiment.

Identification of protein-protein and ribonucleoprotein complexes containing Hfq.

Hfq is a RNA-binding protein that plays a pivotal role in the control of gene expression in bacteria by stabilizing sRNAs and facilitating their pairing with multiple target mRNAs. It has already been shown that Hfq, directly or indirectly, interacts with many proteins: RNase E, Rho, poly(A)polymerase, RNA polymerase… In order to detect more Hfq-related protein-protein interactions we have used two approaches, TAP-tag combined with RNase A treatment to access the role of RNA in these complexes, and protein-protein crosslinking, which freezes protein-protein complexes formed in vivo. In addition, we have performed microscale thermophoresis to evaluate the role of RNA in some of the complexes detected and used far-western blotting to confirm some protein-protein interactions.

Ziconotide for spinal cord injury-related pain.

Background: Central neuropathic pain related to spinal cord injury is notoriously difficult to treat. So far most pharmacological and surgical options have shown but poor results. Recently ziconotide has been approved for use both neuropathic and non-neuropathic pain.

Structural characterization of B. subtilis m1A22 tRNA methyltransferase TrmK: insights into tRNA recognition.

1-Methyladenosine (m1A) is a modified nucleoside found at positions 9, 14, 22 and 58 of tRNAs, which arises from the transfer of a methyl group onto the N1-atom of adenosine. The yqfN gene of Bacillus subtilis encodes the methyltransferase TrmK (BsTrmK) responsible for the formation of m1A22 in tRNA. Here, we show that BsTrmK displays a broad substrate specificity, and methylates seven out of eight tRNA isoacceptor families of B.

[Capsaicin Cutaneous Patch: a Cost-consequences Study in a French University Hospital].

Introduction: The capsaïcine 8% cutaneous patch (Qutenza®) was recently approved for the management of patients with peripheral neuropathic pain (PNP). Considering its limited clinical efficacy data, its improvement of medical benefit was determined to be 5 which was insufficient to support its reimbursement in addition to diagnosis related groups'tarifs. Nevertheless its commercialization was associated with a marked interest considering the unmet therapeutic needs for patients with PNP.

Pleiotropic role of the RNA chaperone protein Hfq in the human pathogen Clostridium difficile.

Clostridium difficile is an emergent human pathogen and the most common cause of nosocomial diarrhea. Our recent data strongly suggest the importance of RNA-based mechanisms for the control of gene expression in C. difficile.

Sequence-structure-function analysis of the bifunctional enzyme MnmC that catalyses the last two steps in the biosynthesis of hypermodified nucleoside mnm5s2U in tRNA.

MnmC catalyses the last two steps in the biosynthesis of 5-methylaminomethyl-2-thiouridine (mnm(5)s(2)U) in tRNA. Previously, we reported that this bifunctional enzyme is encoded by the yfcK open reading frame in the Escherichia coli K12 genome. However, the mechanism of its activity, in particular the potential structural and functional dependence of the domains responsible for catalyzing the two modification reactions, remains unknown.

Mutations in residues involved in zinc binding in the catalytic site of Escherichia coli threonyl-tRNA synthetase confer a dominant lethal phenotype.

Escherichia coli threonyl-tRNA synthetase is a homodimeric protein that acts as both an enzyme and a regulator of gene expression: the protein aminoacylates tRNA(Thr) isoacceptors and binds to its own mRNA, inhibiting its translation. The enzyme contains a zinc atom in its active site, which is essential for the recognition of threonine. Mutations in any of the three amino acids forming the zinc-binding site inactivate the enzyme and have a dominant negative effect on growth if the corresponding genes are placed on a multicopy plasmid.

Achieving error-free translation; the mechanism of proofreading of threonyl-tRNA synthetase at atomic resolution.

The fidelity of aminoacylation of tRNA(Thr) by the threonyl-tRNA synthetase (ThrRS) requires the discrimination of the cognate substrate threonine from the noncognate serine. Misacylation by serine is corrected in a proofreading or editing step. An editing site has been located 39 A away from the aminoacylation site.

Identification of a bifunctional enzyme MnmC involved in the biosynthesis of a hypermodified uridine in the wobble position of tRNA.

The gene encoding the bifunctional enzyme MnmC that catalyzes the two last steps in the biosynthesis of 5-methylaminomethyl-2-thiouridine (mnm5s2U) in tRNA has been previously mapped at about 50 min on the Escherichia coli K12 chromosome, but to date the identity of the corresponding enzyme has not been correlated with any of the known open reading frames (ORFs). Using the protein fold-recognition approach, we predicted that the 74-kDa product of the yfcK ORF located at 52.6 min and annotated as "putative peptidase" comprises a methyltransferase domain and a FAD-dependent oxidoreductase domain.

The modular structure of Escherichia coli threonyl-tRNA synthetase as both an enzyme and a regulator of gene expression.

In addition to its role in tRNA aminoacylation, Escherichia coli threonyl-tRNA synthetase is a regulatory protein which binds a site, called the operator, located in the leader of its own mRNA and inhibits translational initiation by competing with ribosome binding. This work shows that the two essential steps of regulation, operator recognition and inhibition of ribosome binding, are performed by different domains of the protein. The catalytic and the C-terminal domain of the protein are involved in binding the two anticodon arm-like structures in the operator whereas the N-terminal domain of the enzyme is responsible for the competition with the ribosome.

Structural basis of translational control by Escherichia coli threonyl tRNA synthetase.

Escherichia coli threonyl-tRNA synthetase (ThrRS) represses the translation of its own messenger RNA by binding to an operator located upstream of the initiation codon. The crystal structure of the complex between the core of ThrRS and the essential domain of the operator shows that the mRNA uses the recognition mode of the tRNA anticodon loop to initiate binding. The final positioning of the operator, upon which the control mechanism is based, relies on a characteristic RNA motif adapted to the enzyme surface.

Crystal structure of isopentenyl diphosphate:dimethylallyl diphosphate isomerase.

Isopentenyl diphosphate:dimethylallyl diphosphate (IPP:DMAPP) isomerase catalyses a crucial activation step in the isoprenoid biosynthesis pathway. This enzyme is responsible for the isomerization of the carbon-carbon double bond of IPP to create the potent electrophile DMAPP. DMAPP then alkylates other molecules, including IPP, to initiate the extraordinary variety of isoprenoid compounds found in nature.

Transfer RNA-mediated editing in threonyl-tRNA synthetase. The class II solution to the double discrimination problem.

Threonyl-tRNA synthetase, a class II synthetase, uses a unique zinc ion to discriminate against the isosteric valine at the activation step. The crystal structure of the enzyme with an analog of seryl adenylate shows that the noncognate serine cannot be fully discriminated at that step. We show that hydrolysis of the incorrectly formed ser-tRNA(Thr) is performed at a specific site in the N-terminal domain of the enzyme.

Zinc ion mediated amino acid discrimination by threonyl-tRNA synthetase.

Accurate translation of the genetic code depends on the ability of aminoacyl-tRNA synthetases to distinguish between similar amino acids. In order to investigate the basis of amino acid recognition and to understand the role played by the zinc ion present in the active site of threonyl-tRNA synthetase, we have determined the crystal structures of complexes of an active truncated form of the enzyme with a threonyl adenylate analog or threonine. The zinc ion is directly involved in threonine recognition, forming a pentacoordinate intermediate with both the amino group and the side chain hydroxyl.

The structure of threonyl-tRNA synthetase-tRNA(Thr) complex enlightens its repressor activity and reveals an essential zinc ion in the active site.

E. coli threonyl-tRNA synthetase (ThrRS) is a class II enzyme that represses the translation of its own mRNA. We report the crystal structure at 2.

The Escherichia coli threonyl-tRNA synthetase gene contains a split ribosomal binding site interrupted by a hairpin structure that is essential for autoregulation.

The expression of the gene encoding Escherichia coli threonyl-tRNA synthetase (ThrRS) is negatively autoregulated at the translational level. ThrRS binds to its own mRNA leader, which consists of four structural and functional domains: the Shine-Dalgarno (SD) sequence and the initiation codon region (domain 1); two upstream hairpins (domains 2 and 4) connected by a single-stranded region (domain 3). Using a combination of in vivo and in vitro approaches, we show here that the ribosome binds to thrS mRNA at two non-contiguous sites: region -12 to +16 comprising the SD sequence and the AUG codon and, unexpectedly, an upstream single-stranded sequence in domain 3.