Search results for "folding"

Structural Tuning and Conformational Stability of Aromatic Oligoamide Foldamers

2017

A series of aromatic oligoamide foldamers with two or three pyridine-2,6-dicarboxamide units as their main folding motifs and varying aromatic building blocks as linkers have been synthetized to study the effects of the structural variation on the folding properties and conformational stability. Crystallographic studies showed that in the solid state the central linker unit either elongates the helices and more open S-shaped conformations, compresses the helices to more compact conformations or acts as a rigid spacer separating the pyridine-2,6-dicarboxamide units, which for their part add the predictability of the conformational properties. Multidimensional NMR studies showed that, even in…

Monitoring elevation variations in leaf phenology of deciduous broadleaf forests from SPOT/VEGETATION time-series

2011

International audience; In mountain forest ecosystems where elevation gradients are prominent, temperature gradient-based phonological variability can be high. However, there are few studies that assess the capability of remote sensing observations to monitor ecosystem phenology along elevation gradients, despite their relevance under climate change. We investigated the potential of medium resolution remotely sensed data to monitor the elevation variations in the seasonal dynamics of a temperate deciduous broadleaf forested ecosystem. Further, we explored the impact of elevation on the onset of spring leafing. This study was based on the analysis of multi-annual time-series of VEGETATION da…

In vivoanalysis of the lumenal binding protein (BiP) reveals multiple functions of its ATPase domain

2007

International audience; The endoplasmic reticulum (ER) chaperone binding protein (BiP) binds exposed hydrophobic regions of misfolded proteins. Cycles of ATP hydrolysis and nucleotide exchange on the ATPase domain were shown to regulate the function of the ligand-binding domain in vitro. Here we show that ATPase mutants of BiP with defective ATP-hydrolysis (T46G) or ATP-binding (G235D) caused permanent association with a model ligand, but also interfered with the production of secretory, but not cytosolic, proteins in vivo. Furthermore, the negative effect of BiP(T46G) on secretory protein synthesis was rescued by increased levels of wild-type BiP, whereas the G235D mutation was dominant. U…

2019

Integral membrane proteins of the aquaporin family facilitate rapid water flux across cellular membranes in all domains of life. Although the water-conducting pore is clearly defined in an aquaporin monomer, all aquaporins assemble into stable tetramers. In order to investigate the role of protomer–protomer interactions, we analyzed the activity of heterotetramers containing increasing fractions of mutated monomers, which have an impaired oligomerization propensity and activity. In order to enforce interaction between the protomers, we designed and analyzed a genetically fused homotetramer of GlpF, the aquaglyceroporin of the bacterium Escherichia coli (E. coli). However, increasing fractio…

Water Structure in Proteins in Solid State Studied by Near Infrared Spectroscopy

2017

Water adsorption in proteins is the crucial process of protein folding and structure stabilizing. Adsorption of water on proteins can be evaluated by near-infrared spectroscopy, a useful technique for observing combination frequency of a water molecule. In this work, albumin, lysozyme, and silk, were used as models for α-helix and β-pleated sheet proteins. Their NIR spectra during water adsorption process were measured by using an NIR spectrometer equipped with a transflectance accessory. Moreover, the quantitative adsorption of water was determined by gravimetric technique. The results indicate that, there are five different NIR absorptions arise from the OH combination frequencies of wate…

NMR Investigation of Structures of G-Protein Coupled Receptor Folding Intermediates

2016

Folding of G-protein coupled receptors (GPCRs) according to the two-stage model (Popot, J. L., and Engelman, D. M. (1990) Biochemistry 29, 4031-4037) is postulated to proceed in 2 steps: partitioning of the polypeptide into the membrane followed by diffusion until native contacts are formed. Herein we investigate conformational preferences of fragments of the yeast Ste2p receptor using NMR. Constructs comprising the first, the first two, and the first three transmembrane (TM) segments, as well as a construct comprising TM1-TM2 covalently linked to TM7 were examined. We observed that the isolated TM1 does not form a stable helix nor does it integrate well into the micelle. TM1 is significant…

Membrane-anchored heat-shock protein 70 (Hsp70) in cancer.

2020

International audience; Hsp70 is a highly conserved and inducible heat shock protein that belongs to the HSP70 family of molecular chaperones and plays a central role in protein homeostasis. The main function of Hsp70 is to protect cells from physiological, pathological and environmental insults, as it assists an ATP-dependent manner the process of protein folding. Since Hsp70 provides critical cell survival functions, cancer cells are assumed to rely on this chaperone. Strong evidence suggests that Hsp70 is upregulated in different type of cancers and is involved in tumor growth, invasion, migration and resistance to anti-cancer therapy. Interestingly, this Hsp70 upregulation induces Hsp70…

Alzheimer's Disease and Molecular Chaperones: Current Knowledge and the Future of Chaperonotherapy

2016

Background: Alzheimer’s disease (AD) is a dementia, a neurodegenerative condition, and a protein-misfolding disease or proteinopathy, characterized by protein deposits, extracellular plaques and intracellular neurofibrillary tangles, which contain the AD’s typical pathological proteins, abnormal [1]-amyloid and hyperphosphorylated tau, respectively, and are located predominantly in the cortex of the frontal, parietal, and temporal brain lobes. What is the role of molecular chaperones in AD? Data indicate that molecular chaperones, also known as Hsp, are involved in AD, probably displaying protective roles and/or acting as pathogenic factors as it occurs in chaperonopathies in which case AD …

L1 syndrome diagnosis complemented with functional analysis of L1CAM variants located to the two N-terminal Ig-like domains

2016

L1CAM gene mutations cause neurodevelopmental disorders collectively termed L1 syndrome. Insufficient information about L1CAM variants complicates clinical prognosis, genetic diagnosis and genetic counseling. We combined clinical data, in silico effect predictions and functional analysis of four L1CAM variants, p.I37N, p.T38M, p.M172I and p.D202Y, located to the two N-terminal Ig-like domains present in five families with symptoms of L1 syndrome. Software tools predicted destabilizing effects of p.I37N and p.D202Y but results for p.T38M and p.M172I were inconsistent. Cell surface expression of mutant proteins L1-T38M, L1-M172I and L1-D202Y was normal. Conversely, L1-I37N accumulated in the …

Structures of collagen IV globular domains: insight into associated pathologies, folding and network assembly

2018

15 páginas, 6 figuras, 1 tabla.