Search results for "Transmembrane"

Biophysical and functional characterization of the human olfactory receptor OR1A1 expressed in a mammalian inducible cell line

2014

International audience; Olfactory receptors (ORs) play a crucial role in detecting the odorant molecules present in the surrounding environment. These receptors, which belong to class A G-protein-coupled receptors, constitute the largest transmembrane protein family in the human genome. Functional studies showed that the OR family includes members that are able to respond to a large set of odorants and members that are activated by a relatively small number of related odorants. To understand the molecular mechanisms that govern the receptor-ligand interactions, we overexpressed the human OR hOR1A1 in a stable tetracycline-inducible HEK293S cell line. This receptor was engineered by insertin…

Enhanced autophagic-lysosomal activity and increased BAG3-mediated selective macroautophagy as adaptive response of neuronal cells to chronic oxidati…

2019

Oxidative stress and a disturbed cellular protein homeostasis (proteostasis) belong to the most important hallmarks of aging and of neurodegenerative disorders. The proteasomal and autophagic-lysosomal degradation pathways are key measures to maintain proteostasis. Here, we report that hippocampal cells selected for full adaptation and resistance to oxidative stress induced by hydrogen peroxide (oxidative stress-resistant cells, OxSR cells) showed a massive increase in the expression of components of the cellular autophagic-lysosomal network and a significantly higher overall autophagic activity. A comparative expression analysis revealed that distinct key regulators of autophagy are upregu…

Transmembrane signaling and cytoplasmic signal conversion by dimeric transmembrane helix 2 and a linker domain of the DcuS sensor kinase

2020

Transmembrane (TM) signaling is a key process of membrane-bound sensor kinases. The C4-dicarboxylate (fumarate) responsive sensor kinase DcuS of Escherichia coli is anchored by TM helices TM1 and TM2 in the membrane. Signal transmission across the membrane relies on the piston-type movement of the periplasmic part of TM2. To define the role of TM2 in TM signaling, we use oxidative Cys cross-linking to demonstrate that TM2 extends over the full distance of the membrane and forms a stable TM homodimer in both the inactive and fumarate-activated state of DcuS. An S186xxxGxxxG194 motif is required for the stability and function of the TM2 homodimer. The TM2 helix further extends on the periplas…

Prooxidative chain transfer activity by thiol groups in biological systems

2020

Cysteine is arguably the best-studied biological amino acid, whose thiol group frequently participates in catalysis or ligand binding by proteins. Still, cysteine's unusual biological distribution has remained mysterious, being strikingly underrepresented in transmembrane domains and on accessible protein surfaces, particularly in aerobic life forms (“cysteine anomaly”). Noting that lipophilic thiols have been used for decades as radical chain transfer agents in polymer chemistry, we speculated that the rapid formation of thiyl radicals in hydrophobic phases might provide a rationale for the cysteine anomaly. Hence, we have investigated the effects of dodecylthiol and related compounds in i…

The expanding functional roles and signaling mechanisms of adhesion G protein-coupled receptors.

2019

The adhesion class of G protein-coupled receptors (GPCRs) is the second largest family of GPCRs (33 members in humans). Adhesion GPCRs (aGPCRs) are defined by a large extracellular N-terminal region that is linked to a C-terminal seven transmembrane (7TM) domain via a GPCR-autoproteolysis inducing (GAIN) domain containing a GPCR proteolytic site (GPS). Most aGPCRs undergo autoproteolysis at the GPS motif, but the cleaved fragments stay closely associated, with the N-terminal fragment (NTF) bound to the 7TM of the C-terminal fragment (CTF). The NTFs of most aGPCRs contain domains known to be involved in cell-cell adhesion, while the CTFs are involved in classical G protein signaling, as well…

2016

Protein export is central for the survival and virulence of intracellular P. falciparum blood stage parasites. To reach the host cell, exported proteins cross the parasite plasma membrane (PPM) and the parasite-enclosing parasitophorous vacuole membrane (PVM), a process that requires unfolding, suggestive of protein translocation. Components of a proposed translocon at the PVM termed PTEX are essential in this phase of export but translocation activity has not been shown for the complex and questions have been raised about its proposed membrane pore component EXP2 for which no functional data is available in P. falciparum. It is also unclear how PTEX mediates trafficking of both, soluble as…

Cooperation of Secondary Transporters and Sensor Kinases in Transmembrane Signalling

2016

Many membrane-bound sensor kinases require accessory proteins for function. The review describes functional control of membrane-bound sensors by transporters. The C4-dicarboxylate sensor kinase DcuS requires the aerobic or anaerobic C4-dicarboxylate transporters DctA or DcuB, respectively, for function and forms DctA/DcuS or DcuB/DcuS sensor complexes. Free DcuS is in the permanent (ligand independent) ON state. The DctA/DcuS and DcuB/DcuS complexes, on the other hand, control expression in response to C4-dicarboxylates. In DctA/DcuS, helix 8b of DctA and the PASC domain of DcuS are involved in interaction. The stimulus is perceived by the extracytoplasmic sensor domain (PASP) of DcuS. The …

Prevalence and severity of nonalcoholic fatty liver disease by transient elastography: Genetic and metabolic risk factors in a general population.

2017

BACKGROUND & AIMS The worldwide spread of obesity is leading to a dramatic increase in the prevalence of nonalcoholic fatty liver disease (NAFLD) and its complications. We aimed to evaluate both prevalence and factors associated with NAFLD in a general population in a Mediterranean area. METHODS We considered 890 consecutive individuals included in the community-based ABCD (Alimentazione, Benessere Cardiovascolare e Diabete) study (ISRCTN15840340). Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were measured with FibroScan. Participants were genotyped for PNPLA3 rs738409 and TM6SF2 rs58542926 variants. RESULTS The prevalence of NAFLD in the cohort was 48%. NAFL…

No pre-zygotic isolation mechanisms between Schistosoma haematobium and Schistosoma bovis parasites: From mating interactions to differential gene ex…

2021

Species usually develop reproductive isolation mechanisms allowing them to avoid interbreeding. These preventive barriers can act before reproduction, “pre-zygotic barriers”, or after reproduction, “post-zygotic barriers”. Pre-zygotic barriers prevent unfavourable mating, while post-zygotic barriers determine the viability and selective success of the hybrid offspring. Hybridization in parasites and the underlying reproductive isolation mechanisms maintaining their genetic integrity have been overlooked. Using an integrated approach this work aims to quantify the relative importance of pre-zygotic barriers in Schistosoma haematobium x S. bovis crosses. These two co-endemic species cause sch…

Treatment with albumin-hydroxyoleic acid complex restores sensorimotor function in rats with spinal cord injury: Efficacy and gene expression regulat…

2017

Sensorimotor dysfunction following incomplete spinal cord injury (SCI) is often characterized by paralysis, spasticity and pain. Previously, we showed that intrathecal (i.t.) administration of the albumin-oleic acid (A-OA) complex in rats with SCI produced partial improvement of these symptoms and that oral 2-hydroxyoleic acid (HOA, a non-hydrolyzable OA analogue), was efficacious in the modulation and treatment of nociception and pain-related anxiety, respectively. Here we observed that intrathecal treatment with the complex albumin-HOA (A-HOA) every 3 days following T9 spinal contusion injury improved locomotor function assessed with the Rotarod and inhibited TA noxious reflex activity in…