Search results for "GroEL"

GroEL buffers against deleterious mutations

2002

GroEL, a heat-shock protein that acts as a molecular chaperone1, is overproduced in endosymbiotic but not in free-living bacteria2,3,4, presumably to assist in the folding of conformationally damaged proteins. Here we show that the overproduction of GroEL in Escherichia coli masks the effects of harmful mutations that have accumulated during a simulated process of vertical transmission. This molecular mechanism, which may be an adaptation to the bacterium's intracellular lifestyle, is able to rescue lineages from a progressive fitness decline resulting from the fixation of deleterious mutations under strong genetic drift5,6.

Adaptive evolution in GroEL from distantly related endosymbiotic bacteria of insects

2005

Many symbioses between bacteria and insects resulted from ancient infections followed by strict vertical transmission within host lineages. The strong bottlenecks under which this transmission occurs promote the neutral fixation of slightly deleterious mutations by genetic drift. As predicted by Muller's ratchet, this fixation will drive endosymbiotic bacteria through an irreversible dynamics of fitness loss. The chaperonin GroEL has been proposed as a compensatory mechanism whereby endosymbiotic bacteria of aphids persist. Here, we show that endosymbiotic bacteria of insects from two phylogenetically very distant bacterial phyla have fixed amino acid substitutions by positive selection in …

Naïve Hsp60, similarly to GroEL, oligomerizes to build heptameric and tetradecameric structures.

2013

The evolution of the heat-shock protein GroEL from Buchnera, the primary endosymbiont of aphids, is governed by positive selection

2002

The heat-shock protein GroEL is a double-ring-structured chaperonin that assists the folding of many newly synthesized proteins in Escherichia coli and the refolding in vitro, with the cochaperonin GroES, of conformationally damaged proteins. This protein is constitutively overexpressed in the primary symbiotic bacteria of many insects, constituting approximately 10% of the total protein in Buchnera, the primary endosymbiont of aphids. In the present study, we perform a maximum likelihood (ML) analysis to unveil the selective constraints in GroEL. In addition, we apply a new statistical approach to determine the patterns of evolution in this highly interesting protein. The main conclusion d…

Hsp60 chaperonopathies and chaperonotherapy: targets and agents

2014

Hsp60 (Cpn60) assembles into a tetradecamer that interacts with the co-chaperonin Hsp10 (Cpn10) to assist client polypeptides to fold, but it also has other roles, including participation in pathogenic mechanisms.Hsp60 chaperonopathies are pathological conditions, inherited or acquired, in which the chaperone plays a determinant etiologic-pathogenic role. These diseases justify selection of Hsp60 as a target for developing agents that interfere with its pathogenic effects. We provide information on how to proceed.The information available encourages the development of ways to improve Hsp60 activity (positive chaperonotherapy) when deficient or to block it (negative chaperonotherapy) when pa…

Quaternary structures of GroEL and naïve-Hsp60 chaperonins in solution: a combined SAXS-MD study

2015

The quaternary structures of bacterial GroEL and human naïve-Hsp60 chaperonins in physiological conditions have been investigated by an innovative approach based on a combination of synchrotron Small Angle X-ray Scattering (SAXS) in-solution experiments and molecular dynamics (MD) simulations. Low-resolution SAXS experiments over large and highly symmetric oligomers are analyzed on the basis of the high-resolution structure of the asymmetric protein monomers, provided by MD. The results reveal remarkable differences between the solution and the crystallographic structure of GroEL and between the solution structures of GroEL and of its human homologue Hsp60.

Detection of Candidatus Neoehrlichia mikurensis in Norway up to the northern limit of Ixodes ricinus distribution using a novel real time PCR test ta…

2019

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Background Candidatus Neoehrlichia mikurensis is an emerging tick-borne pathogen. It is widely distributed in Ixodes ricinus ticks in Europe, but knowledge of its distribution in Norway, where I. ricinus reaches its northern limit, is limited. In this study we have developed a real time PCR test for Ca. N. mikurensis and used it to invest…

The Molecular Anatomy of Human Hsp60 and its Similarity with that of Bacterial Orthologs and Acetylcholine Receptor Reveal a Potential Pathogenetic R…

2012

Heat-shock protein 60 (Hsp60) is ubiquitous and highly conserved being present in eukaryotes and prokaryotes, including pathogens. This chaperonin, although typically a mitochondrial protein, can also be found in other intracellular sites, extracellularly, and in circulation. Thus, it can signal the immune system and participate in the development of inflammation and immune reactions. Both phenomena can be elicited by human and foreign Hsp60 (e.g., bacterial GroEL), when released into the blood by infectious agents. Consequently, all these Hsp60 proteins become part of a complex autoimmune response characterized by multiple cross reactions because of their structural similarities. In this s…

Fitness Trade-Offs Determine the Role of the Molecular Chaperonin GroEL in Buffering Mutations

2015

Molecular chaperones fold many proteins and their mutated versions in a cell and can sometimes buffer the phenotypic effect of mutations that affect protein folding. Unanswered questions about this buffering include the nature of its mechanism, its influence on the genetic variation of a population, the fitness trade-offs constraining this mechanism, and its role in expediting evolution. Answering these questions is fundamental to understand the contribution of buffering to increase genetic variation and ecological diversification. Here, we performed experimental evolution, genome resequencing, and computational analyses to determine the trade-offs and evolutionary trajectories of Escherich…

A comparative analysis of the products of GROEL-1 gene fromChlamydia trachomatisserovar D and the HSP60 var1 transcript fromHomo sapienssuggests a po…

2009

Summary Chlamydia trachomatis serovar D produces large quantities of HSP60-1 during infections, which accumulate inside the host cell inducing autoimmunity. We compare the aminoacid sequences of the human HSP60 with the bacterial counterpart to better elucidate how CTHSP60 may simulate HSP60 from human origin during infection and may induce an autoimmune response. As a result of the comparison we suggest several possible epitopes of the CTHSP60, which may induce autoimmunity.