Search results for "chaperone"
showing 10 items of 249 documents
Chaperones: General Characteristics and Classifications
2013
This chapter presents the classification of chaperones, their molecular properties among which that of forming functional complexes involving various molecules, and their distribution inside and outside the cell. The chaperone genes in the human genome are listed and briefly described, focusing on the small heat-shock proteins (sHsp), Hsp60, Hsp70, and Hsp90, and mentioning all others known. The chapter also introduces the concept of chaperoning system, i.e., the physiological system of an organism which is composed of all its chaperones, co-chaperones, and chaperone co-factors.
CtsR is the master regulator of stress response gene expression in Oenococcus oeni.
2005
ABSTRACT Although many stress response genes have been characterized in Oenococcus oeni , little is known about the regulation of stress response in this malolactic bacterium. The expression of eubacterial stress genes is controlled both positively and negatively at the transcriptional level. Overall, negative regulation of heat shock genes appears to be more widespread among gram-positive bacteria. We recently identified an ortholog of the ctsR gene in O. oeni . In Bacillus subtilis , CtsR negatively regulates expression of the clp genes, which belong to the class III family of heat shock genes. The ctsR gene of O. oeni is cotranscribed with the downstream clpC gene. Sequence analysis of t…
Myelin pathology: Involvement of molecular chaperones and the promise of chaperonotherapy
2019
The process of axon myelination involves various proteins including molecular chaperones. Myelin alteration is a common feature in neurological diseases due to structural and functional abnormalities of one or more myelin proteins. Genetic proteinopathies may occur either in the presence of a normal chaperoning system, which is unable to assist the defective myelin protein in its folding and migration, or due to mutations in chaperone genes, leading to functional defects in assisting myelin maturation/migration. The latter are a subgroup of genetic chaperonopathies causing demyelination. In this brief review, we describe some paradigmatic examples pertaining to the chaperonins Hsp60 (HSPD1,…
Endoplasmic reticulum‐resident chaperones modulate the inflammatory and angiogenic responses of endothelial cells
2015
SummaryBackground Wound healing depends on a well-balanced regulation of inflammation and angiogenesis. In chronic wounds the healing process is disturbed and inflammation persists. Regulation of wound closure is controlled by transmembrane and extracellular proteins, the folding and maturation of which occur in the endoplasmic reticulum (ER) by ER-resident chaperone machinery. Objectives To study the role of the ER-resident chaperones BiP/Grp78, its cochaperone Mdg1/ERdJ4, and Grp94 in chronic, nonhealing wounds. Methods Immunohistochemical staining of these chaperones in individual human biopsies and investigation of the possible role of BiP and Mdg1 in endothelial cells, focusing on thei…
Reorganization of Nuclear Domain 10 Induced by Papillomavirus Capsid Protein L2
2002
AbstractNuclear domains (ND) 10 are associated with proteins implicated in transcriptional regulation, growth suppression, and apoptosis. We now show that the minor capsid protein L2 of human papillomavirus (HPV) type 33 induces a reorganization of ND10-associated proteins. Whereas the promyelocytic leukemia protein, the major structural component of ND10, was unaffected by L2, Sp100 was released from ND10 upon L2 expression. The total cellular amount of Sp100, but not of Sp100 mRNA, decreased significantly, suggesting degradation of Sp100. Proteasome inhibitors induced the dispersal of Sp100 and inhibited the nuclear translocation of L2. In contrast to Sp100, Daxx was recruited to ND10 by …
Heat shock and Cd2+ exposure regulate PML and Daxx release from ND10 by independent mechanisms that modify the induction of heat-shock proteins 70 an…
2003
Nuclear domains called ND10 or PML bodies might function as nuclear depots by recruiting or releasing certain proteins. Although recruitment of proteins through interferon-induced upregulation and SUMO-1 modification level of PML had been defined, it is not known whether release of proteins is regulated and has physiological consequences. Exposure to sublethal environmental stress revealed a sequential release of ND10-associated proteins. Upon heat shock Daxx and Sp100 were released but PML remained, whereas exposure to subtoxic concentrations of CdCl2 induced the release of ND10-associated proteins, including PML, with Sp100 remaining in a few sites. In both cases,recovery times were simil…
Decipher the mechanisms of protein conformational changes induced by nucleotide binding through free-energy landscape analysis: ATP binding to Hsp70.
2013
ATP regulates the function of many proteins in the cell by transducing its binding and hydrolysis energies into protein conformational changes by mechanisms which are challenging to identify at the atomic scale. Based on molecular dynamics (MD) simulations, a method is proposed to analyze the structural changes induced by ATP binding to a protein by computing the effective free-energy landscape (FEL) of a subset of its coordinates along its amino-acid sequence. The method is applied to characterize the mechanism by which the binding of ATP to the nucleotide-binding domain (NBD) of Hsp70 propagates a signal to its substrate-binding domain (SBD). Unbiased MD simulations were performed for Hsp…
Human Inducible Hsp70: Structures, Dynamics, and Interdomain Communication from All-Atom Molecular Dynamics Simulations
2015
The 70 kDa human heat shock protein is a major molecular chaperone involved in de novo folding of proteins in vivo and refolding of proteins under stress conditions. Hsp70 is related to several "misfolding diseases" and other major pathologies, such as cancer, and is a target for new therapies. Hsp70 is comprised of two main domains: an N-terminal nucleotide binding domain (NBD) and a C-terminal substrate protein binding domain (SBD). The chaperone function of Hsp70 is based on an allosteric mechanism. Binding of ATP in NBD decreases the affinity of the substrate for SBD, and hydrolysis of ATP is promoted by binding of polypeptide segments in the SBD. No complete structure of human Hsp70 is…
A constitutive 70 kDa heat-shock protein is localized on the fibres of spindles and asters at metaphase in an ATP-dependent manner: A new chaperone r…
2001
In the present study, double immunofluorescence and immunoblot analysis have been used to show that centrosomes, isolated from Paracentrotus lividus sea urchin embryos at the first mitotic metaphase, contain the constitutive chaperone, heat-shock protein (HSP) 70. More specifically, we demonstrate that centrosomes contain only the HSP70-d isoform, which is one of the four isoforms identified in P. lividus . We also provide evidence that p34(cell division control kinase-2) and t complex polypeptide-1 (TCP-1) α, a subunit of the TCP-1 complex, are localized on the centrosomes. Furthermore, inhibition of TCP-1 in vivo, via microinjecting an anti-(TCP-1α) antibody into P. lividus eggs before fe…
The Role of Molecular Chaperones in Virus Infection and Implications for Understanding and Treating COVID-19
2020
The COVID-19 pandemic made imperative the search for means to end it, which requires a knowledge of the mechanisms underpinning the multiplication and spread of its cause, the coronavirus SARS-CoV-2. Many viruses use members of the hosts’ chaperoning system to infect the target cells, replicate, and spread, and here we present illustrative examples. Unfortunately, the role of chaperones in the SARS-CoV-2 cycle is still poorly understood. In this review, we examine the interactions of various coronaviruses during their infectious cycle with chaperones in search of information useful for future research on SARS-CoV-2. We also call attention to the possible role of molecular mimicry in the dev…