Search results for "Protein folding"
showing 10 items of 196 documents
Polar/Ionizable Residues in Transmembrane Segments: Effects on Helix-Helix Packing
2012
The vast majority of membrane proteins are anchored to biological membranes through hydrophobic alpha-helices. Sequence analysis of high-resolution membrane protein structures show that ionizable amino acid residues are present in transmembrane (TM) helices, often with a functional and/or structural role. Here, using as scaffold the hydrophobic TM domain of the model membrane protein glycophorin A (GpA), we address the consequences of replacing specific residues by ionizable amino acids on TM helix insertion and packing, both in detergent micelles and in biological membranes. Our findings demonstrate that ionizable residues are stably inserted in hydrophobic environments, and tolerated in t…
Investigation of Phosphorylation-Induced Folding of an Intrinsically Disordered Protein by Coarse-Grained Molecular Dynamics
2021
Apart from being the most common mechanism of regulating protein function and transmitting signals throughout the cell, phosphorylation has an ability to induce disorder-to-order transition in an intrinsically disordered protein. In particular, it was shown that folding of the intrinsically disordered protein, eIF4E-binding protein isoform 2 (4E-BP2), can be induced by multisite phosphorylation. Here, the principles that govern the folding of phosphorylated 4E-BP2 (pT37pT46 4E-BP2(18–62)) are investigated by analyzing canonical and replica exchange molecular dynamics trajectories, generated with the coarse-grained united-residue force field, in terms of local and global motions and the time…
Human apolipoprotein A-I natural variants: molecular mechanisms underlying amyloidogenic propensity
2012
Human apolipoprotein A-I (apoA-I)-derived amyloidosis can present with either wild-type (Wt) protein deposits in atherosclerotic plaques or as a hereditary form in which apoA-I variants deposit causing multiple organ failure. More than 15 single amino acid replacement amyloidogenic apoA-I variants have been described, but the molecular mechanisms involved in amyloid-associated pathology remain largely unknown. Here, we have investigated by fluorescence and biochemical approaches the stabilities and propensities to aggregate of two disease-associated apoA-I variants, apoA-IGly26Arg, associated with polyneuropathy and kidney dysfunction, and apoA-ILys107-0, implicated in amyloidosis in severe…
Strategies for the production of difficult-to-express full-length eukaryotic proteins using microbial cell factories : production of human alpha-gala…
2015
This work was supported by ERANET-IB08-007 project from the European Union and its linked national project EUI2008- 03610 to AV. We also appreciate the support from EME2007-08 to NFM from Universitat Autonoma de Barcelona, from Antartide 2010 to MLT and EP, from MIUR Azioni Integrate Italia-Spagna 2010 Prot. IT10LECLM9 to MLT, from MINECO (IT2009-0021) to AV and LT, from AGAUR (2009SGR-108) to AV. AV is also supported by The Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN, Spain), an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Car…
Solvent-induced free energy landscape and solute-solvent dynamic coupling in a multielement solute
1999
AbstractMolecular dynamics simulations using a simple multielement model solute with internal degrees of freedom and accounting for solvent-induced interactions to all orders in explicit water are reported. The potential energy landscape of the solute is flat in vacuo. However, the sole untruncated solvent-induced interactions between apolar (hydrophobic) and charged elements generate a rich landscape of potential of mean force exhibiting typical features of protein landscapes. Despite the simplicity of our solute, the depth of minima in this landscape is not far in size from free energies that stabilize protein conformations. Dynamical coupling between configurational switching of the syst…
Effective approach for calculations of absolute stability of proteins using focused dielectric constants
2009
The ability to predict the absolute stability of proteins based on their corresponding sequence and structure is a problem of great fundamental and practical importance. In this work, we report an extensive, refinement and validation of our recent approach (Roca et al., FEBS Lett 2007;581:2065-2071) for predicting absolute values of protein stability DeltaG(fold). This approach employs the semimacroscopic protein dipole Langevin dipole method in its linear response approximation version (PDLD/S-LRA) while using the best fitted values of the dielectric constants epsilon'(p) and epsilon'(eff) for the self energy and charge-charge interactions, respectively. The method is validated on a divers…
New set of 2D/3D thermodynamic indices for proteins. A formalism based on "Molten Globule" theory
2010
Abstract We define eight new macromolecular indices, and several related descriptors for proteins. The coarse grained methodology used for its deduction ensures its fast execution and becomes a powerful potential tool to explore large databases of protein structures. The indices are intended for stability studies, predicting Φ -values, predicting folding rate constants, protein QSAR/QSPR as well as protein alignment studies. Also, these indices could be used as scoring function in protein-protein docking or 3D protein structure prediction algorithms and any others applications which need a numerical code for proteins and/or residues from 2D or 3D format.
The role of heat shock proteins in neoplastic processes and the research on their importance in the diagnosis and treatment of cancer
2021
Heat shock proteins (HSPs) are chaperones with highly conservative primary structure, necessary in the processes of protein folding to the most energetically advantageous conformation and maintaining their stability. HSPs perform a number of important functions in various cellular processes and are capable of modulating pathophysiological conditions at the cellular and systemic levels. An example is the high level of HSP expression in neoplastic tissues, which disrupts the apoptosis of transformed cells and promotes the processes of proliferation, invasion, and metastasis. In addition, an increasing amount of information is appearing about the participation of HSPs in the formation of multi…
Chaperonopathies of senescence and the scrambling of interactions between the chaperoning and the immune systems
2010
Aging entails progressive deterioration of molecules and supramolecular structures, including Hsp chaperones and their complexes, paralleled by functional decline. Recent research has changed our views on Hsp chaperones. They work inside and outside cells in many locations, alone or forming teams, interacting with cells, receptors, and molecules that are not chaperones, in roles that are not typically attributed to chaperones, such as protein folding. Hsp chaperones form a physiological system with a variety of functions and interactions with other systems, for example, the immune system. We propose that chaperone malfunctioning due to structural damage or gene dysregulation during aging ha…
Interaction of explicit solvent with hydrophobic/philic/charged residues of a protein: Residue character vs. conformational context
1998
Molecular dynamics simulations of model solutes in explicit molecular water have recently elicited novel aspects of the strong nonpair additivity of the potential of mean force (PMF) and related solvent-induced forces (SIFs) and hydration. Here we present the results of the same type of work on SIFs acting on bovine pancreatic trypsin inhibitor (BPTI) at single residue/sidechain resolution. In this system, nonpair additivity and the consequent dependence of SIFs on the protein conformational context are sufficiently strong to overturn SIFs on some individual residues, relative to expectations based on their individual characters. This finding calls for a revisitation and offers a richer and…