Crowbars and ratchets: Hsp100 chaperones as tools in reversing protein aggregation

2001 ◽  
Vol 79 (5) ◽  
pp. 557-568 ◽  
Author(s):  
John R Glover ◽  
John M Tkach

Molecular chaperones have the capacity to prevent inappropriate interactions between aggregation-prone folding or unfolding intermediates created in the cell during protein synthesis or in response to physical and chemical stress. What happens when surveillance by molecular chaperones is evaded or overwhelmed and aggregates accumulate? Recent progress in the elucidation of Hsp100/Clp function suggests that intracellular aggregates or stable complexes can be progressively dissolved by the action of chaperones that act as molecular crowbars or ratchets. These insights set the stage for new progress in the understanding and treatment of diseases of protein folding.Key words: molecular chaperone, Hsp100, aggregation, amyloid.

2019 ◽  
Vol 10 (32) ◽  
pp. 7484-7495 ◽  
Author(s):  
Huadong Yuan ◽  
Tiefeng Liu ◽  
Yujing Liu ◽  
Jianwei Nai ◽  
Yao Wang ◽  
...  

This review summarizes recent progress of biomass-derived materials in Li–S batteries. These materials are promising due to their advantages including strong physical and chemical adsorption, high abundance, low cost, and environmental friendliness.


2019 ◽  
Vol 14 (5) ◽  
pp. 1800523
Author(s):  
Hyeon‐Jung Yang ◽  
Kyung‐Ho Lee ◽  
Hye Jin Lim ◽  
Dong‐Myung Kim

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Depeng Wang ◽  
Shufang Zhao ◽  
Ruiyang Yin ◽  
Linlin Li ◽  
Zheng Lou ◽  
...  

AbstractDiversified regulation of electrons have received much attention to realize a multi-functional transistor, and it is crucial to have a considerable control over the charge carriers in transistors. Ionic gel, as the dielectric material in transistors, facilitates a large capacitance, and high induced-carrier concentrations. This review presents the recent progress in ionic-gated transistors (IGTs) that have good mechanical stability as well as high physical and chemical stability. We first briefly introduce the various applications of IGTs in sensors, neuromorphic transistors, organic transistor circuits, and health detection. Finally, the future perspectives of IGTs are discussed and some possible solutions to the challenges are also proposed.


2021 ◽  
Vol 22 (7) ◽  
pp. 3700
Author(s):  
Junna Hayashi ◽  
Jennifer Ton ◽  
Sparsh Negi ◽  
Daniel E. K. M. Stephens ◽  
Dean L. Pountney ◽  
...  

Oxidation of the neurotransmitter, dopamine (DA), is a pathological hallmark of Parkinson’s disease (PD). Oxidized DA forms adducts with proteins which can alter their functionality. αB-crystallin and Hsp27 are intracellular, small heat-shock molecular chaperone proteins (sHsps) which form the first line of defense to prevent protein aggregation under conditions of cellular stress. In vitro, the effects of oxidized DA on the structure and function of αB-crystallin and Hsp27 were investigated. Oxidized DA promoted the cross-linking of αB-crystallin and Hsp27 to form well-defined dimer, trimer, tetramer, etc., species, as monitored by SDS-PAGE. Lysine residues were involved in the cross-links. The secondary structure of the sHsps was not altered significantly upon cross-linking with oxidized DA but their oligomeric size was increased. When modified with a molar equivalent of DA, sHsp chaperone functionality was largely retained in preventing both amorphous and amyloid fibrillar aggregation, including fibril formation of mutant (A53T) α-synuclein, a protein whose aggregation is associated with autosomal PD. In the main, higher levels of sHsp modification with DA led to a reduction in chaperone effectiveness. In vivo, DA is sequestered into acidic vesicles to prevent its oxidation and, intracellularly, oxidation is minimized by mM levels of the antioxidant, glutathione. In vitro, acidic pH and glutathione prevented the formation of oxidized DA-induced cross-linking of the sHsps. Oxidized DA-modified αB-crystallin and Hsp27 were not cytotoxic. In a cellular context, retention of significant chaperone functionality by mildly oxidized DA-modified sHsps would contribute to proteostasis by preventing protein aggregation (particularly of α-synuclein) that is associated with PD.


2008 ◽  
Vol 410 (3) ◽  
pp. 439-453 ◽  
Author(s):  
Laurence H. Pearl ◽  
Chrisostomos Prodromou ◽  
Paul Workman

The molecular chaperone Hsp90 (90 kDa heat-shock protein) is a remarkably versatile protein involved in the stress response and in normal homoeostatic control mechanisms. It interacts with ‘client proteins’, including protein kinases, transcription factors and others, and either facilitates their stabilization and activation or directs them for proteasomal degradation. By this means, Hsp90 displays a multifaceted ability to influence signal transduction, chromatin remodelling and epigenetic regulation, development and morphological evolution. Hsp90 operates as a dimer in a conformational cycle driven by ATP binding and hydrolysis at the N-terminus. The cycle is also regulated by a group of co-chaperones and accessory proteins. Here we review the biology of the Hsp90 molecular chaperone, emphasizing recent progress in our understanding of structure–function relationships and the identification of new client proteins. In addition we describe the exciting progress that has been made in the development of Hsp90 inhibitors, which are now showing promise in the clinic for cancer treatment. We also identify the gaps in our current understanding and highlight important topics for future research.


2019 ◽  
Vol 20 (9) ◽  
pp. 2323 ◽  
Author(s):  
Jongho Jeon

In the last two decades, various nanomaterials have attracted increasing attention in medical science owing to their unique physical and chemical characteristics. Incorporating radionuclides into conventionally used nanomaterials can confer useful additional properties compared to the original material. Therefore, various radionuclides have been used to synthesize functional nanomaterials for biomedical applications. In particular, several α- or β-emitter-labeled organic and inorganic nanoparticles have been extensively investigated for efficient and targeted cancer treatment. This article reviews recent progress in cancer therapy using radiolabeled nanomaterials including inorganic, polymeric, and carbon-based materials and liposomes. We first provide an overview of radiolabeling methods for preparing anticancer agents that have been investigated recently in preclinical studies. Next, we discuss the therapeutic applications and effectiveness of α- or β-emitter-incorporated nanomaterials in animal models and the emerging possibilities of these nanomaterials in cancer therapy.


MRS Advances ◽  
2017 ◽  
Vol 3 (1-2) ◽  
pp. 1-11
Author(s):  
Chengzhi Luo ◽  
Chunxu Pan

ABSTRACTCarbon nanotubes (CNTs) possess superior mechanical, physical and chemical properties that make them ideal candidates for making sensors. However, challenges restricting their widespread applications in sensors still exist. To make the CNTs-based sensors own higher performance, nature has offered us with scientific and technological clues from the formation of biological composites using common organic components via naturally mild approaches. This paper reviews the recent progress on the bio-inspired synthesis of the CNTs-based sensors and their unique structures and novel properties.


2004 ◽  
Vol 32 (5) ◽  
pp. 733-737 ◽  
Author(s):  
W. Wintermeyer ◽  
F. Peske ◽  
M. Beringer ◽  
K.B. Gromadski ◽  
A. Savelsbergh ◽  
...  

Protein synthesis in the cell is performed on ribosomes, large ribonucleoprotein particles, which in bacteria consist of three RNA molecules and over 50 proteins. This review summarizes recent progress in understanding the mechanisms of the elongation phase of protein synthesis. Results from rapid kinetic analysis of elongation reactions are discussed in the light of recent structural data.


2018 ◽  
Vol 6 (27) ◽  
pp. 12932-12944 ◽  
Author(s):  
Jingxia Wu ◽  
Zhiyong Pan ◽  
Ye Zhang ◽  
Bingjie Wang ◽  
Huisheng Peng

Nitrogen-doping represents a general and effective method in adjusting the physical and chemical properties of carbon nanomaterials. The recent progress in the synthesis of nitrogen-doped carbon nanomaterials and their applications in batteries are carefully discussed with a focus on their electrochemical properties.


2005 ◽  
Vol 33 (4) ◽  
pp. 551-552 ◽  
Author(s):  
B. Kalmar ◽  
D. Kieran ◽  
L. Greensmith

Neurodegenerative diseases are characterized by a number of common hallmarks, such as the presence of intracellular aggregates and activation of the apoptotic cell-death pathway. Intracellular chaperones, responsible for protein integrity and structural repair, may play a crucial role in the progression of a disease. In this paper, we aim to summarize our understanding of the role and potential of a particular family of chaperones, the heat-shock proteins, in neurodegeneration, by focusing our discussion on models of motoneuron death.


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