A human CCT5 gene mutation causing distal neuropathy impairs hexadecamer assembly in an archaeal model

Antonino Lauria, Anna Maria Almerico, Francesco Cappello, Haibin Luo, Francesca Angileri, Maruda Shanmugasundaram, Wonki Min, Everly Conway De Macario, Igor K. Lednev, Francesco Cappello, Frank T. Robb, Alberto J.L. Macario

Risultato della ricerca: Articlepeer review

13 Citazioni (Scopus)

Abstract

Chaperonins mediate protein folding in a cavity formed by multisubunit rings. The human CCT has eightnon-identical subunits and the His147Arg mutation in one subunit, CCT5, causes neuropathy. Knowledgeis scarce on the impact of this and other mutations upon the chaperone’s structure and functions. To makeprogress, experimental models must be developed. We used an archaeal mutant homolog and demonstratedthat the His147Arg mutant has impaired oligomeric assembly, ATPase activity, and defective proteinhomeostasis functions. These results establish for the first time that a human chaperonin gene defect can bereproduced 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 comparedwith the human counterpart, in which just one subunit per ring is defective. Therefore, the slight deficit of anon-lethal mutation can be detected and characterized.
Lingua originaleEnglish
pagine (da-a)1-9
Numero di pagine9
RivistaScientific Reports
Volume4
Stato di pubblicazionePublished - 2014

All Science Journal Classification (ASJC) codes

  • ???subjectarea.asjc.1000???

Fingerprint

Entra nei temi di ricerca di 'A human CCT5 gene mutation causing distal neuropathy impairs hexadecamer assembly in an archaeal model'. Insieme formano una fingerprint unica.

Cita questo