Missense Mutations of Human Hsp60: A Computational Analysis to Unveil Their Pathological Significance
Author
Vitale, Alessandra MariaConway de Macario, Everly

Alessandro, Riccardo
Cappello, Francesco
Macario, Alberto J.L.
Marino Gammazza, Antonella
Date
2020-08-18Journal
Frontiers in GeneticsPublisher
Frontiers Media S.A.Type
Article
Metadata
Show full item recordAbstract
Two chaperonopathies have been linked to mutations in the human hsp60 (hHsp60; HSPD1) gene, but other existing variants might cause diseases, even if there is no comprehensive information about this possibility. To fill this vacuum, which might be at the basis of misdiagnoses or simply ignorance of chaperonopathies in patients who would benefit by proper identification of their ailments, we searched the sequenced human genomes available in public databases to determine the range of missense mutations in the single hsp60 gene. A total of 224 missense mutations were identified, including those already characterized. Detailed examination of these mutations was carried out to assess their possible impact on protein structure-function, considering: (a) the properties of individual amino acids; (b) the known functions of the amino acids in the human Hsp60 and/or in the highly similar bacterial ortholog GroEL; (c) the location of the mutant amino acids in the monomers and oligomers; and (d) structure-function relationships inferred from crystal structures. And we also applied a bioinformatics tool for predicting the impact of mutations on proteins. A portion of these genetic variants could have a deleterious impact on protein structure-function, but have not yet been associated with any pathology. Are these variants causing disease with mild clinical manifestations and are, therefore, being overlooked? Or are they causing overt disease, which is misdiagnosed? Our data indicate that more chaperonopathies might occur than is currently acknowledged and that awareness of chaperonopathies among medical personnel will increase their detection and improve patient management.Sponsors
Ministero dello Sviluppo EconomicoKeyword
chaperoning systemHsp60 gene variants
Hsp60 genetic chaperonopathies
human genomes
underdiagnosed chaperonopathies
Identifier to cite or link to this item
http://hdl.handle.net/10713/13692ae974a485f413a2113503eed53cd6c53
10.3389/fgene.2020.00969