title: A human CCT5 gene mutation causing distal neuropathy impairs hexadecamer assembly in an archaeal model.
abstract: Chaperonins mediate protein folding in a cavity formed by multisubunit rings. The human CCT has eight non-identical subunits and the His147Arg mutation in one subunit, CCT5, causes neuropathy. Knowledge is scarce on the impact of this and other mutations upon the chaperone's structure and functions. To make progress, experimental models must be developed. We used an archaeal mutant homolog and demonstrated that the His147Arg mutant has impaired oligomeric assembly, ATPase activity, and defective protein homeostasis functions. These results establish for the first time that a human chaperonin gene defect can be reproduced and studied at the molecular level with an archaeal homolog. The major advantage of the system, consisting of rings with eight identical subunits, is that it amplifies the effects of a mutation as compared with the human counterpart, in which just one subunit per ring is defective. Therefore, the slight deficit of a non-lethal mutation can be detected and characterized.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore; and Institute of Marine and Environmental Technology (IMET); Columbus Center, Baltimore, MD 21201, USA.
authors.forename: Wonki
authors.initials: W
authors.lastname: Min
authors.affiliation: 1] Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore; and Institute of Marine and Environmental Technology (IMET); Columbus Center, Baltimore, MD 21201, USA [2] Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Angileri
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore; and Institute of Marine and Environmental Technology (IMET); Columbus Center, Baltimore, MD 21201, USA.
authors.forename: Haibin
authors.initials: H
authors.lastname: Luo
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Sezione di Chimica Farmaceutica e Biologica. University of Palermo, Palermo, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Lauria
authors.affiliation: Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222, USA.
authors.forename: Maruda
authors.initials: M
authors.lastname: Shanmugasundaram
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Sezione di Chimica Farmaceutica e Biologica. University of Palermo, Palermo, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Almerico
authors.affiliation: 1] Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche (BIONEC), University of Palermo, Palermo, Italy [2] Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cappello
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore; and Institute of Marine and Environmental Technology (IMET); Columbus Center, Baltimore, MD 21201, USA.
authors.forename: Everly Conway
authors.initials: EC
authors.lastname: de Macario
authors.affiliation: Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222, USA.
authors.forename: Igor K
authors.initials: IK
authors.lastname: Lednev
authors.affiliation: 1] Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore; and Institute of Marine and Environmental Technology (IMET); Columbus Center, Baltimore, MD 21201, USA [2] Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
authors.forename: Alberto J L
authors.initials: AJ
authors.lastname: Macario
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore; and Institute of Marine and Environmental Technology (IMET); Columbus Center, Baltimore, MD 21201, USA.
authors.forename: Frank T
authors.initials: FT
authors.lastname: Robb
mesh_terms: D000595:Amino Acid Sequence; D001105:Archaea / Q000235:genetics*; D056404:Chaperonin Containing TCP-1 / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D016415:Sequence Alignment; D013816:Thermodynamics
chemical_list: C533301:CCT5 protein, human; D056404:Chaperonin Containing TCP-1