1. A Multipronged Method for Unveiling Subtle Structural-Functional Defects of Mutant Chaperone Molecules Causing Human Chaperonopathies
- Author
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Donatella, Bulone, Pier Luigi, San Biagio, Tatiana, Quiñones-Ruiz, Manuel, Rosario-Alomar, Igor K, Lednev, Frank T, Robb, Everly, Conway de Macario, and Alberto J L, Macario
- Subjects
Amyloid ,Hot Temperature ,Calorimetry, Differential Scanning ,Protein Stability ,Archaeal Proteins ,Alkaline Phosphatase ,Microscopy, Atomic Force ,Recombinant Proteins ,Pyrococcus furiosus ,Penaeidae ,Malate Dehydrogenase ,Mutation ,Animals ,Humans ,Protein Processing, Post-Translational ,Molecular Chaperones - 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.
- Published
- 2018