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

  • Donatella Bulone
  • Pier Luigi San Biagio
  • Tatiana Quiñones-Ruiz
  • Manuel Rosario-Alomar
  • Igor K. Lednev
  • Frank T. Robb
  • Everly Conway de Macario
  • Alberto J. L. MacarioEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1873)


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.


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



Part of the work by PLSB and DB was carried out using instruments funded by PO. FESR 2007/2013 “Piattaforma regionale di ricerca traslazionale per la salute” 4.1.2. Asse IV. We thank Drs. A. Provenzano and F. Impallari for technical support.

Part of this work was carried out at the Biomolecular Labeling Laboratory-National Institute of Standards and Technology (NIST), Rockville, USA. FTR, ECdeM, and AJLM thank Zvi Kelman for his hospitality and stimulating discussions.

FTR was supported by NSF USA grants EAR0747394, EAR0747412, and MCB0605301; and Air Force Office of Scientific Research under Grants AFOSR 03-S-28900; and 496 9550-10-1-0272 (IKL and FTR). IKL was supported in part by the National Science Foundation under Grant No. CHE-1152752 (I.K.L.). AJLM and ECdeM were partially supported by IMET. This work was done under the agreement between IEMEST (Italy) and IMET (USA) (IMET contribution number IMET 18-003).


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Donatella Bulone
    • 1
  • Pier Luigi San Biagio
    • 1
  • Tatiana Quiñones-Ruiz
    • 2
  • Manuel Rosario-Alomar
    • 2
  • Igor K. Lednev
    • 2
  • Frank T. Robb
    • 3
    • 4
  • Everly Conway de Macario
    • 3
    • 5
  • Alberto J. L. Macario
    • 3
    • 5
    Email author
  1. 1.Institute of Biophysics, SL PalermoNational Research CouncilPalermoItaly
  2. 2.Department of ChemistryUniversity at Albany, SUNYAlbanyUSA
  3. 3.Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore-Institute of Marine and Environmental Technology (IMET)BaltimoreUSA
  4. 4.Institute for Bioscience and Biotechnology Research (IBBR)RockvilleUSA
  5. 5.Euro-Mediterranean Institute of Science and Technology (IEMEST)PalermoItaly

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