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Cellular and Molecular Neurobiology

, Volume 32, Issue 6, pp 943–947 | Cite as

The Molecular Anatomy of Human Hsp60 and its Similarity with that of Bacterial Orthologs and Acetylcholine Receptor Reveal a Potential Pathogenetic Role of Anti-Chaperonin Immunity in Myasthenia Gravis

  • Antonella Marino GammazzaEmail author
  • Fabio Bucchieri
  • Luigi M. E. Grimaldi
  • Arcangelo Benigno
  • Everly Conway de Macario
  • Alberto J. L. Macario
  • Giovanni Zummo
  • Francesco Cappello
Short Communication

Abstract

Heat-shock protein 60 (Hsp60) is ubiquitous and highly conserved being present in eukaryotes and prokaryotes, including pathogens. This chaperonin, although typically a mitochondrial protein, can also be found in other intracellular sites, extracellularly, and in circulation. Thus, it can signal the immune system and participate in the development of inflammation and immune reactions. Both phenomena can be elicited by human and foreign Hsp60 (e.g., bacterial GroEL), when released into the blood by infectious agents. Consequently, all these Hsp60 proteins become part of a complex autoimmune response characterized by multiple cross reactions because of their structural similarities. In this study, we demonstrate that Hsp60 proteins from humans and two common pathogens, Chlamydia trachomatis and Chlamydia pneumoniae, share various sequence segments of potentially highly immunogenic epitopes with acetylcholine receptor α1 subunit (AChRα1). The structural data indicate that AChRα1 antibodies, implicated in the pathogenesis of myasthenia gravis, could very well be elicited and/or maintained by self- and/or bacterial Hsp60.

Keywords

Shared epitopes Molecular mimicry Autoimmunity Neuromuscular disorder 

Notes

Acknowledgments

This study was partially supported by the University of Palermo Italy (FC and GZ), and the Istituto Euro-Mediterraneo di Scienza e Tecnologia, Palermo, Italy (FC and AJLM).

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Antonella Marino Gammazza
    • 1
    • 2
    Email author
  • Fabio Bucchieri
    • 1
    • 2
  • Luigi M. E. Grimaldi
    • 3
  • Arcangelo Benigno
    • 1
  • Everly Conway de Macario
    • 4
  • Alberto J. L. Macario
    • 2
    • 4
  • Giovanni Zummo
    • 1
  • Francesco Cappello
    • 1
    • 2
  1. 1.Dipartimento di Biomedicina Sperimentale e Neuroscienze ClinicheUniversità degli Studi di PalermoPalermoItaly
  2. 2.Istituto Euro-Mediterraneo di Scienza e Tecnologia (IEMEST)PalermoItaly
  3. 3.Fondazione Istituto San Raffaele “G. Giglio”CefalùPalermo
  4. 4.Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore, and IMETBaltimoreUSA

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