scholarly journals Role of ATP on the Interaction of α-Crystallin with Its Substrates and Its Implications for the Molecular Chaperone Function

2004 ◽  
Vol 279 (41) ◽  
pp. 42648-42657 ◽  
Author(s):  
Ashis Biswas ◽  
Kali P. Das
Keyword(s):  
Molecular Chaperone ◽  
Chaperone Function

scholarly journals Enzyme activity after resealing within ghost erythrocyte cells, and protection by α-crystallin against fructose-induced inactivation

2002 ◽  
Vol 368 (3) ◽  
pp. 865-874 ◽  
Author(s):  
Barry K. DERHAM ◽  
John J. HARDING
Keyword(s):  
Enzyme Activity ◽  
Molecular Chaperone ◽  
Soluble Fraction ◽  
Erythrocyte Ghosts ◽  
Ghost Cell ◽  
Chaperone Function ◽  
Zero Time ◽  
Soluble Fractions

The role of α-crystallin as a molecular chaperone has been shown in many in vitro studies. In the present paper, we report on the chaperone function of α-crystallin within resealed erythrocyte ghosts. Eight enzymes were individually resealed within erythrocyte ghosts and assayed at zero time and at 24h. The ghost cell suspension was separated into soluble and membrane fractions. Five of the enzymes had significantly greater enzyme activity after 24h than the control within the soluble fractions. Fructation caused a decrease in enzyme activity (relative to the control). Resealing of α-crystallin within the ghost cell alongside the enzymes protected against inactivation by fructose within the soluble fraction.

Molecular function of the prolyl cis/trans isomerase and metallochaperone SlyD

2013 ◽  
Vol 394 (8) ◽  
pp. 965-975 ◽  
Author(s):  
Michael Kovermann ◽  
Franz X. Schmid ◽  
Jochen Balbach
Keyword(s):  
Molecular Chaperone ◽  
Molecular Basis ◽  
Catalytic Efficiency ◽  
Enzyme Mechanism ◽  
Molecular Function ◽  
Twin Arginine Translocation ◽  
Chaperone Function ◽  
Nickel Binding ◽  
Biophysical Analysis ◽  
Optimal Function

Abstract SlyD is a bacterial two-domain protein that functions as a molecular chaperone, a prolyl cis/trans isomerase, and a nickel-binding protein. This review summarizes recent findings about the molecular enzyme mechanism of SlyD. The chaperone function located in one domain of SlyD is involved in twin-arginine translocation and increases the catalytic efficiency of the prolyl cis/trans isomerase domain in protein folding by two orders of magnitude. The C-terminal tail of SlyD binds Ni2+ ions and supplies them for the maturation of [NiFe] hydrogenases. A combined biochemical and biophysical analysis revealed the molecular basis of the delicate interplay of the different domains of SlyD for optimal function.

scholarly journals Role of salt bridges in the dimer interface of 14-3-3ζ in dimer dynamics, N-terminal α-helical order, and molecular chaperone activity

2017 ◽  
Vol 293 (1) ◽  
pp. 89-99 ◽  
Author(s):  
Joanna M. Woodcock ◽  
Katy L. Goodwin ◽  
Jarrod J. Sandow ◽  
Carl Coolen ◽  
Matthew A. Perugini ◽  
...  
Keyword(s):  
Molecular Chaperone ◽  
Chaperone Activity ◽  
Salt Bridges ◽  
Dimer Interface

scholarly journals Effects of modifications of α-crystallin on its chaperone and other properties

2002 ◽  
Vol 364 (3) ◽  
pp. 711-717 ◽  
Author(s):  
Barry K. DERHAM ◽  
John J. HARDING
Keyword(s):  
Congenital Cataract ◽  
Point Mutations ◽  
Small Heat Shock Protein ◽  
High Molecular Mass ◽  
Lens Crystallins ◽  
Post Translational Modifications ◽  
Chaperone Function ◽  
Arginine Residues

The role of α-crystallin, a small heat-shock protein and chaperone, may explain how the lens stays transparent for so long. α-Crystallin prevents the aggregation of other lens crystallins and proteins that have become unfolded by ‘trapping’ the protein in a high-molecular-mass complex. However, during aging, the chaperone function of α-crystallin becomes compromised, allowing the formation of light-scattering aggregates that can proceed to form cataracts. Within the central part of the lens there is no turnover of damaged protein, and therefore post-translational modifications of α-crystallin accumulate that can reduce chaperone function; this is compounded in cataract lenses. Extensive in vitro glycation, carbamylation and oxidation all decrease chaperone ability. In the present study, we report the effect of the modifiers malondialdehyde, acetaldehyde and methylglyoxal, all of which are pertinent to cataract. Also modification by aspirin, which is known to delay cataract and other diseases, has been investigated. Recently, two point mutations of arginine residues were shown to cause congenital cataract. 1,2-Cyclohexanedione modifies arginine residues, and the extent of modification needed for a change in chaperone function was investigated. Only methylglyoxal and extensive modification by 1,2-cyclohexanedione caused a decrease in chaperone function. This highlights the robust nature of α-crystallin.

scholarly journals Role of the Helical Protrusion in the Conformational Change and Molecular Chaperone Activity of the Archaeal Group II Chaperonin

2004 ◽  
Vol 279 (18) ◽  
pp. 18834-18839 ◽  
Author(s):  
Ryo Iizuka ◽  
Sena So ◽  
Tomonao Inobe ◽  
Takao Yoshida ◽  
Tamotsu Zako ◽  
...  
Keyword(s):  
Conformational Change ◽  
Molecular Chaperone ◽  
Chaperone Activity ◽  
Group Ii ◽  
Group Ii Chaperonin

Genetic analysis of Hsp90 function in Cryptococcus neoformans highlights key roles in stress tolerance and virulence

Genetics ◽  
2021 ◽  
Author(s):  
Ci Fu ◽  
Sarah R Beattie ◽  
Andrew J Jezewski ◽  
Nicole Robbins ◽  
Luke Whitesell ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cryptococcus Neoformans ◽  
Molecular Chaperone ◽  
Fungal Pathogens ◽  
Genetic Characterization ◽  
Great Promise ◽  
Report Generation ◽  
Conditional Expression ◽  
Expression Strain

Abstract The opportunistic human fungal pathogen Cryptococcus neoformans has tremendous impact on global health, causing 181,000 deaths annually. Current treatment options are limited, and the frequent development of drug resistance exacerbates the challenge of managing invasive cryptococcal infections. In diverse fungal pathogens, the essential molecular chaperone Hsp90 governs fungal survival, drug resistance, and virulence. Therefore, targeting this chaperone has emerged as a promising approach to combat fungal infections. However, the role of Hsp90 in supporting C. neoformans pathogenesis remains largely elusive due to a lack of genetic characterization. To help dissect the functions of Hsp90 in C. neoformans, we generated a conditional expression strain in which HSP90 is under control of the copper-repressible promoter CTR4-2. Addition of copper to culture medium depleted Hsp90 transcript and protein levels in this strain, resulting in compromised fungal growth at host temperature; increased sensitivity to stressors, including the azole class of antifungals; altered C. neoformans morphology; and impaired melanin production. Finally, leveraging the fact that copper concentrations vary widely in different mouse tissues, we demonstrated attenuated virulence for the CTR4-2p-HSP90 mutant specifically in an inhalation model of Cryptococcus infection. During invasion and establishment of infection in this mouse model, the pathogen is exposed to the relatively high copper concentrations found in the lung as compared to blood. Overall, this work generates a tractable genetic system to study the role of Hsp90 in supporting the pathogenicity of C. neoformans and provides proof-of-principle that targeting Hsp90 holds great promise as a strategy to control cryptococcal infection. Article Summary Hsp90 is a conserved molecular chaperone that modulates virulence traits and drug resistance in fungal pathogens. Despite the potential of Hsp90 as a target for antifungal development, genetic characterization remains lacking in Cryptococcus neoformans. Here, we report generation of a C. neoformans HSP90 conditional expression strain. Utilizing this genetic tool, we found depletion of Hsp90 impacted tolerance to environmental stresses, growth at physiological temperature, and virulence in vivo. Thus, we suggest targeting Hsp90 is a viable strategy for treating cryptococcosis.

Structure, stability, and chaperone function of αA-crystallin: Role of N-terminal region

Biopolymers ◽  
2007 ◽  
Vol 86 (3) ◽  
pp. 177-192 ◽  
Author(s):  
Madhuchhanda Kundu ◽  
P. C. Sen ◽  
K. P. Das
Keyword(s):  
Terminal Region ◽  
Structure Stability ◽  
Chaperone Function
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