title: 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.
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.
authors.affiliation: Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Palermo, Italy. antonella.marino@hotmail.it
authors.forename: Antonella Marino
authors.initials: AM
authors.lastname: Gammazza
authors.forename: Fabio
authors.initials: F
authors.lastname: Bucchieri
authors.forename: Luigi M E
authors.initials: LM
authors.lastname: Grimaldi
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Benigno
authors.forename: Everly Conway
authors.initials: EC
authors.lastname: de Macario
authors.forename: Alberto J L
authors.initials: AJ
authors.lastname: Macario
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zummo
authors.forename: Francesco
authors.initials: F
authors.lastname: Cappello
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D018834:Chaperonin 60 / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007109:Immunity / Q000276:immunology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000276:immunology*; D017433:Protein Structure, Secondary; D011950:Receptors, Cholinergic / Q000737:chemistry* / Q000276:immunology; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D018834:Chaperonin 60; D011950:Receptors, Cholinergic