Search results for "DOMAINS"

Identification and structural characterization of LytU, a unique peptidoglycan endopeptidase from the lysostaphin family

2017

AbstractWe introduce LytU, a short member of the lysostaphin family of zinc-dependent pentaglycine endopeptidases. It is a potential antimicrobial agent for S. aureus infections and its gene transcription is highly upregulated upon antibiotic treatments along with other genes involved in cell wall synthesis. We found this enzyme to be responsible for the opening of the cell wall peptidoglycan layer during cell divisions in S. aureus. LytU is anchored in the plasma membrane with the active part residing in the periplasmic space. It has a unique Ile/Lys insertion at position 151 that resides in the catalytic site-neighbouring loop and is vital for the enzymatic activity but not affecting the …

Phosphorylated immunoreceptor tyrosine-based activation motifs and integrin cytoplasmic domains activate spleen tyrosine kinase via distinct mechanis…

2018

Spleen tyrosine kinase (Syk) is involved in cellular adhesion and also in the activation and development of hematopoietic cells. Syk activation induced by genomic rearrangement has been linked to certain T-cell lymphomas, and Syk inhibitors have been shown to prolong survival of patients with B-cell lineage malignancies. Syk is activated either by its interaction with a double-phosphorylated immunoreceptor tyrosine-based activation motif (pITAM), which induces rearrangements in the Syk structure, or by the phosphorylation of specific tyrosine residues. In addition to its immunoreceptor function, Syk is activated downstream of integrin pathways, and integrins bind to the same region in Syk a…

Structural Basis of the High Affinity Interaction between the Alphavirus Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2

2016

We show that a peptide from Chikungunya virus nsP3 protein spanning residues 1728–1744 binds the amphiphysin-2 (BIN1) Src homology-3 (SH3) domain with an unusually high affinity (Kd 24 nM). Our NMR solution complex structure together with isothermal titration calorimetry data on several related viral and cellular peptide ligands reveal that this exceptional affinity originates from interactions between multiple basic residues in the target peptide and the extensive negatively charged binding surface of amphiphysin-2 SH3. Remarkably, these arginines show no fixed conformation in the complex structure, indicating that a transient or fluctuating polyelectrostatic interaction accounts for this …

Do genetic polymorphisms in angiotensin converting enzyme 2 (ACE2) gene play a role in coronavirus disease 2019 (COVID-19)?

2020

Abstract Although some demographic, clinical and environmental factors have been associated with a higher risk of developing coronavirus disease 2019 (COVID-19) and progressing towards severe disease, altogether these variables do not completely account for the different clinical presentations observed in patients with comparable baseline risk, whereby some subjects may remain totally asymptomatic, whilst others develop a very aggressive illness. Some predisposing genetic backgrounds can hence potentially explain the broad inter-individual variation of disease susceptibility and/or severity. It has been now clearly established that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2…

Viral entry, lipid rafts and caveosomes.

2005

Lipid rafts and caveolae are detergent-insoluble plasma membrane microdomains, involved in cellular endocytic processes and signalling. Several viruses, including a human pathogen, echovirus 1, and an extensively studied simian virus 40 utilize these domains for internalization into the host cells. Interaction of viruses with receptors on the cell surface triggers specific conformational changes of the virus particle and can give rise to signalling events, which determine the mechanisms of virus entry. After internalization via cell surface lipid rafts or caveolae, virus-containing vesicles can fuse with caveosomes, pre-existing cytoplasmic organelles, or dock on other intracellular organel…

AFM study of interaction forces in supported planar DPPC bilayers in the presence of general anesthetic halothane

2006

International audience; In spite of numerous investigations, the molecular mechanism of general anesthetics action is still not well understood. It has been shown that the anesthetic potency is related to the ability of an anesthetic to partition into the membrane. We have investigated changes in structure, dynamics and forces of interaction in supported dipalmitoylphosphatidylcholine (DPPC) bilayers in the presence of the general anesthetic halothane. In the present study, we measured the forces of interaction between the probe and the bilayer using an atomic force microscope. The changes in force curves as a function of anesthetic incorporation were analyzed. Force measurements were in go…

MAST-RT0 SOLUTION OF 3D NAVIER STOKES EQUATIONS ON UNSTRUCTURED MESHS. PRELIMINARY RESULTS IN THE LAMINAR CASE

2021

MAST-RT0 solution of 3D Navier Stokes equations in very irregular domains. Preliminary results in the laminar case

2021

A new numerical methodology to solve the 3D Navier-Stokes equations for incompressible fluids within complex boundaries and unstructured body-fitted tetrahedral mesh is presented and validated with three literature and one real-case tests. We apply a fractional time step procedure where a predictor and a corrector problem are sequentially solved. The predictor step is solved applying the MAST (Marching in Space and Time) procedure, which explicitly handles the non-linear terms in the momentum equations, allowing numerical stability for Courant number greater than one. Correction steps are solved by a Mixed Hybrid Finite Elements discretization that assumes positive distances among tetrahedr…

Down-regulation of Endogenous Amyloid Precursor Protein Processing due to Cellular Aging

2005

Processing of amyloid precursor protein (APP) is a well acknowledged central pathogenic mechanism in Alzheimer disease. However, influences of age-associated cellular alterations on the biochemistry of APP processing have not been studied in molecular detail so far. Here, we report that processing of endogenous APP is down-regulated during the aging of normal human fibroblasts (IMR-90). The generation of intracellular APP cleavage products C99, C83, and AICD gradually declines with increasing life span and is accompanied by a reduced secretion of soluble APP (sAPP) and sAPPalpha. Further, the maturation of APP was reduced in senescent cells, which has been shown to be directly mediated by a…

Trichuris trichiura egg extract proteome reveals potential diagnostic targets and immunomodulators.

2021

The proteomic analysis was performed at the proteomics facility of SCSIE, University of Valencia (Burjassot, Spain) that belongs to ProteoRed, PRB2-ISCIII, Madrid, Spain. We also thank Dr. Tatiana Corey, Dr. Amy Beierschmitt and Dr. Pompei Bolfa for their support during sample collection.