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Trends in Microbiology May 2001SecB is a molecular chaperone unique to the phylum Proteobacteria, which includes the majority of known Gram-negative bacteria of medical, industrial and agricultural... (Review)
Review
SecB is a molecular chaperone unique to the phylum Proteobacteria, which includes the majority of known Gram-negative bacteria of medical, industrial and agricultural significance. SecB is involved in the translocation of secretory proteins across the cytoplasmic membrane. The crystal structure of the Haemophilus influenzae SecB provides new insights into how SecB simultaneously recognizes its two ligands: unfolded preproteins and SecA, the ATPase subunit of the translocase. SecB uses its entire molecular surface for these two functions, but for preprotein release and its own membrane release, SecB relies on the catalytic activity of SecA. This defines SecB as a translocation-specific molecular chaperone.
Topics: Adenosine Triphosphatases; Bacterial Proteins; Binding Sites; Carrier Proteins; Escherichia coli Proteins; Haemophilus influenzae; Membrane Transport Proteins; Models, Molecular; Molecular Chaperones; Protein Binding; Protein Structure, Quaternary; SEC Translocation Channels; SecA Proteins
PubMed: 11336818
DOI: 10.1016/s0966-842x(01)01980-1 -
Trends in Biochemical Sciences Jan 1996Hsp47 is a novel stress protein in the endoplasmic reticulum that binds specifically to various types of collagens and procollagens. Hsp47 transiently associates with... (Review)
Review
Hsp47 is a novel stress protein in the endoplasmic reticulum that binds specifically to various types of collagens and procollagens. Hsp47 transiently associates with procollagen and is involved in collagen processing and/or secretion under normal conditions. Under conditions of stress, Hsp47 is part of the quality control system for procollagen, including the prevention of the secretion of procollagen with abnormal conformation. In addition to its role as a molecular chaperone, Hsp47 synthesis always parallels that of collagen in developing tissues and various cell lines, and in collagen-related pathological conditions such as fibrosis.
Topics: Animals; Collagen; HSP47 Heat-Shock Proteins; Heat-Shock Proteins; Humans; Molecular Chaperones
PubMed: 8848834
DOI: 10.1016/0968-0004(96)80881-4 -
International Journal of Cosmetic... Feb 2011Molecular chaperone, heat shock proteins (HSPs), stabilizes intracellular processes of cells under stress. Little is known about the role of molecular chaperone proteins... (Review)
Review
A survey and analysis of the role of molecular chaperone proteins and imidazole-containing dipeptide-based compounds as molecular escorts into the skin during stress, injury, water structuring and other types of cutaneous pathophysiology.
Molecular chaperone, heat shock proteins (HSPs), stabilizes intracellular processes of cells under stress. Little is known about the role of molecular chaperone proteins in the skin pathology, rejuvenation and wound healing, or whether their expression is altered by environmental and physiological stress to the skin or systemic disease. The focus of this study was to examine the role of molecular chaperone proteins in the skin's local response to wounding, skin ageing and a range of skin diseases. Free radicals, one form of insult, induce or contribute to adverse effects on the skin, including erythema, oedema, wrinkling, photoaging, inflammation, autoimmune reactions, hypersensitivity, keratinization abnormalities, preneoplastic lesions and skin cancer. A unified view of the molecular and cellular pathogenesis of the skin age-related pathology conditions has led to the search for molecular and chemical chaperones that can slow, arrest or revert disease progression. Specific alpha-crystallin domains and pharmacological imidazole-containing dipeptide chaperone molecules are now emerging that link our biophysical insights with developed skin therapeutic techniques. In this article, we discuss the molecular nature of the stress signals, the mechanisms that underlie activation of the heat shock response, the role of molecular chaperone proteins as skin protective molecules, and strategies for pharmacologically active chaperone molecules and their imidazole-containing dipeptide inducers as regulators of the skin stress response. We discuss how impairment in protein hydration may cause ultrastructural, mechanical and biochemical changes in structural proteins in the aged skin. We have pioneered the molecular chaperone protein activated therapeutic or cosmetic platform to enable simultaneous analysis of water-binding and structuring characteristics for biology of skin ageing and skin disease-related pathways. This cutting-edge technology has improved the way that proteins hydrate in photoaged skin. The mechanisms of skin diseases, ageing, cellular, and signalling pathways mediated by targeting with molecular chaperone protein(s) in patented formulations with imidazole containing dipeptide (N-acetylcarnosine, carcinine, carnosine) are also discussed within this review.
Topics: Cosmetics; Data Collection; Dipeptides; Humans; Imidazoles; Molecular Chaperones; Skin; Stress, Physiological; Water
PubMed: 20546050
DOI: 10.1111/j.1468-2494.2010.00601.x -
Biochimica Et Biophysica Acta Mar 2012Cellular environments are highly complex and contain a copious variety of proteins that must operate in unison to achieve homeostasis. To guide and preserve order,... (Review)
Review
Cellular environments are highly complex and contain a copious variety of proteins that must operate in unison to achieve homeostasis. To guide and preserve order, multifaceted molecular chaperone networks are present within each cell type. To handle the vast client diversity and regulatory demands, a wide assortment of chaperones are needed. In addition to the classic heat shock proteins, cochaperones with inherent chaperoning abilities (e.g., p23, Hsp40, Cdc37, etc.) are likely used to complete a system. In this review, we focus on the HSP90-associated cochaperones and provide evidence supporting a model in which select cochaperones are used to differentially modulate target proteins, contribute to combinatorial client regulation, and increase the overall reach of a cellular molecular chaperone network. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90).
Topics: HSP90 Heat-Shock Proteins; Humans; Molecular Chaperones; Protein Binding; Signal Transduction
PubMed: 21889547
DOI: 10.1016/j.bbamcr.2011.08.011 -
Sub-cellular Biochemistry 2023Molecular chaperones and their associated co-chaperones are essential in health and disease as they are key facilitators of protein-folding, quality control and... (Review)
Review
Molecular chaperones and their associated co-chaperones are essential in health and disease as they are key facilitators of protein-folding, quality control and function. In particular, the heat-shock protein (HSP) 70 and HSP90 molecular chaperone networks have been associated with neurodegenerative diseases caused by aberrant protein-folding. The pathogenesis of these disorders usually includes the formation of deposits of misfolded, aggregated protein. HSP70 and HSP90, plus their co-chaperones, have been recognised as potent modulators of misfolded protein toxicity, inclusion formation and cell survival in cellular and animal models of neurodegenerative disease. Moreover, these chaperone machines function not only in folding but also in proteasome-mediated degradation of neurodegenerative disease proteins. This chapter gives an overview of the HSP70 and HSP90 chaperones, and their respective regulatory co-chaperones, and explores how the HSP70 and HSP90 chaperone systems form a larger functional network and its relevance to counteracting neurodegenerative disease associated with misfolded proteins and disruption of proteostasis.
Topics: Animals; HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins; Molecular Chaperones; Neurodegenerative Diseases; Protein Folding
PubMed: 36520314
DOI: 10.1007/978-3-031-14740-1_13 -
Journal of Microbiology (Seoul, Korea) Nov 2022Pseudomonas is widespread in various environmental and host niches. To promote rejuvenation, cellular protein homeostasis must be finely tuned in response to diverse... (Review)
Review
Pseudomonas is widespread in various environmental and host niches. To promote rejuvenation, cellular protein homeostasis must be finely tuned in response to diverse stresses, such as extremely high and low temperatures, oxidative stress, and desiccation, which can result in protein homeostasis imbalance. Molecular chaperones function as key components that aid protein folding and prevent protein denaturation. Pseudomonas, an ecologically important bacterial genus, includes human and plant pathogens as well as growth-promoting symbionts and species useful for bioremediation. In this review, we focus on protein quality control systems, particularly molecular chaperones, in ecologically diverse species of Pseudomonas, including the opportunistic human pathogen Pseudomonas aeruginosa, the plant pathogen Pseudomonas syringae, the soil species Pseudomonas putida, and the psychrophilic Pseudomonas antarctica.
Topics: Humans; Pseudomonas syringae; Molecular Chaperones; Pseudomonas aeruginosa; Plants; Biodegradation, Environmental
PubMed: 36318358
DOI: 10.1007/s12275-022-2425-0 -
Molecular and Cellular Biochemistry Sep 1994Starvation of mouse hepatoma cells for essential amino acids or glucose results in the ADP-ribosylation of the molecular chaperone BiP/GRP78. Addition of the missing... (Review)
Review
Starvation of mouse hepatoma cells for essential amino acids or glucose results in the ADP-ribosylation of the molecular chaperone BiP/GRP78. Addition of the missing nutrient to the medium reverses the reaction. The signal mediating the response to environmental nutrients involves the translational efficiency. An inhibitor of proteins synthesis, cycloheximide, or reduced temperature, both of which reduce translational efficiency, stimulate the ADP-ribosylation of BiP/GRP78. Inhibition of N-linked glycosylation of proteins results in the overproduction of BiP/GRP78. The over produced protein is not ADP-ribosylated suggesting that this is the functional form of BiP/GRP78. The over produced BiP/GRP78 can, however, be ADP-ribosylated if the cells are starved for an essential amino acid. BiP/GRP78 resides in the lumen of the endoplasmic reticulum where it participates in the assembly of secretory and integral membrane proteins. ADP-ribosylation of BiP/GRP78 during starvation is probably part of a nutritional stress response which conserves limited nutrients by slowing flow through the secretory pathway.
Topics: Adenosine Diphosphate Ribose; Animal Nutritional Physiological Phenomena; Animals; Carrier Proteins; Endoplasmic Reticulum Chaperone BiP; Heat-Shock Proteins; Immunoglobulin Heavy Chains; Molecular Chaperones; Tumor Cells, Cultured
PubMed: 7898457
DOI: 10.1007/BF00928456 -
Seminars in Cell & Developmental Biology Apr 2015Protein homeostasis (proteostasis) is essential for maintaining the functionality of the proteome. The disruption of proteostasis, due to genetic mutations or an... (Review)
Review
Protein homeostasis (proteostasis) is essential for maintaining the functionality of the proteome. The disruption of proteostasis, due to genetic mutations or an age-related decline, leads to aberrantly folded proteins that typically lose their function. The accumulation of misfolded and aggregated protein is also cytotoxic and has been implicated in the pathogenesis of neurodegenerative diseases. Neurons have developed an intrinsic protein quality control network, of which molecular chaperones are an essential component. Molecular chaperones function to promote efficient folding and target misfolded proteins for refolding or degradation. Increasing molecular chaperone expression can suppress protein aggregation and toxicity in numerous models of neurodegenerative disease; therefore, molecular chaperones are considered exciting therapeutic targets. Furthermore, mutations in several chaperones cause inherited neurodegenerative diseases. In this review, we focus on the importance of molecular chaperones in neurodegenerative diseases, and discuss the advances in understanding their protective mechanisms.
Topics: Animals; Heat-Shock Proteins; Humans; Molecular Chaperones; Neurodegenerative Diseases; Protein Aggregation, Pathological; Proteins
PubMed: 25770416
DOI: 10.1016/j.semcdb.2015.03.003 -
JCI Insight Mar 2022Molecular chaperones are responsible for maintaining cellular homeostasis, and one such chaperone, GRP170, is an endoplasmic reticulum (ER) resident that oversees both...
Molecular chaperones are responsible for maintaining cellular homeostasis, and one such chaperone, GRP170, is an endoplasmic reticulum (ER) resident that oversees both protein biogenesis and quality control. We previously discovered that GRP170 regulates the degradation and assembly of the epithelial sodium channel (ENaC), which reabsorbs sodium in the distal nephron and thereby regulates salt-water homeostasis and blood pressure. To define the role of GRP170 - and, more generally, molecular chaperones in kidney physiology - we developed an inducible, nephron-specific GRP170-KO mouse. Here, we show that GRP170 deficiency causes a dramatic phenotype: profound hypovolemia, hyperaldosteronemia, and dysregulation of ion homeostasis, all of which are associated with the loss of ENaC. Additionally, the GRP170-KO mouse exhibits hallmarks of acute kidney injury (AKI). We further demonstrate that the unfolded protein response (UPR) is activated in the GRP170-deficient mouse. Notably, the UPR is also activated in AKI when originating from various other etiologies, including ischemia, sepsis, glomerulonephritis, nephrotic syndrome, and transplant rejection. Our work establishes the central role of GRP170 in kidney homeostasis and directly links molecular chaperone function to kidney injury.
Topics: Acute Kidney Injury; Animals; Endoplasmic Reticulum Stress; HSP70 Heat-Shock Proteins; Mice; Molecular Chaperones
PubMed: 35104250
DOI: 10.1172/jci.insight.151869 -
The Journal of Biological Chemistry Jul 2017Here, we provide an overview of the different mechanisms whereby three different chaperones, Spy, Hsp70, and Hsp60, interact with folding proteins, and we discuss how... (Comparative Study)
Comparative Study Review
Here, we provide an overview of the different mechanisms whereby three different chaperones, Spy, Hsp70, and Hsp60, interact with folding proteins, and we discuss how these chaperones may guide the folding process. Available evidence suggests that even a single chaperone can use many mechanisms to aid in protein folding, most likely due to the need for most chaperones to bind clients promiscuously. Chaperone mechanism may be better understood by always considering it in the context of the client's folding pathway and biological function.
Topics: Animals; Chaperonin 60; Dimerization; Escherichia coli Proteins; HSP70 Heat-Shock Proteins; Humans; Models, Molecular; Molecular Chaperones; Periplasmic Proteins; Protein Conformation; Protein Folding; Protein Interaction Domains and Motifs
PubMed: 28620048
DOI: 10.1074/jbc.R117.796862