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Methods Mol Biol. 2019;1873:69-92. doi: 10.1007/978-1-4939-8820-4_5.

A Multipronged Method for Unveiling Subtle Structural-Functional Defects of Mutant Chaperone Molecules Causing Human Chaperonopathies.

Author information

1
Institute of Biophysics, SL Palermo, National Research Council, Palermo, Italy.
2
Department of Chemistry, University at Albany, SUNY, Albany, NY, USA.
3
Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore-Institute of Marine and Environmental Technology (IMET), Baltimore, MD, USA.
4
Institute for Bioscience and Biotechnology Research (IBBR), Rockville, MD, USA.
5
Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
6
Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore-Institute of Marine and Environmental Technology (IMET), Baltimore, MD, USA. ajlmacario@som.umaryland.edu.
7
Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy. ajlmacario@som.umaryland.edu.

Abstract

Chaperonopathies are diseases in which abnormal chaperones play an etiopathogenic role. A chaperone is mutated or otherwise abnormal (e.g., modified by an aberrant posttranslational modification) in structure/function. To understand the pathogenic mechanisms of chaperonopathies, it is necessary to elucidate the impact of the pathogenic mutation or posttranslational modification on the chaperone molecule's properties and functions. This impact is usually subtle because if it were more than subtle the overall effect on the cell and organism would be catastrophic, lethal. This is because most chaperones are essential for life and, if damaged in structure/function too strongly, there would be death of the cell/organism, and no phenotype, i.e., there would be no patients with chaperonopathies. Consequently, diagnostic procedures and analysis of defects of the abnormal chaperones require a multipronged method for assessing the chaperone molecule from various angles. Here, we present such a method that includes assessing the intrinsic properties and the chaperoning functions of chaperone molecules.

KEYWORDS:

Calorimetry; Chaperoning functions; Chaperonopathies; Fibril dispersion; Genetic chaperonopathies; Heat protection; Molecular properties; Multipronged method; Mutant chaperones; Subtle changes

PMID:
30341604
DOI:
10.1007/978-1-4939-8820-4_5
[Indexed for MEDLINE]

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