title: The C-terminal region of the human p23 chaperone modulates its structure and function.
abstract: The p23 protein is a chaperone widely involved in protein homeostasis, well known as an Hsp90 co-chaperone since it also controls the Hsp90 chaperone cycle. Human p23 includes a β-sheet domain, responsible for interacting with Hsp90; and a charged C-terminal region whose function is not clear, but seems to be natively unfolded. p23 can undergo caspase-dependent proteolytic cleavage to form p19 (p231-142), which is involved in apoptosis, while p23 has anti-apoptotic activity. To better elucidate the function of the human p23 C-terminal region, we studied comparatively the full-length human p23 and three C-terminal truncation mutants: p23₁₋₁₁₇; p23₁₋₁₃₁ and p23₁₋₁₄₂. Our data indicate that p23 and p19 have distinct characteristics, whereas the other two truncations behave similarly, with some differences to p23 and p19. We found that part of the C-terminal region can fold in an α-helix conformation and slightly contributes to p23 thermal-stability, suggesting that the C-terminal interacts with the β-sheet domain. As a whole, our results suggest that the C-terminal region of p23 is critical for its structure-function relationship. A mechanism where the human p23 C-terminal region behaves as an activation/inhibition module for different p23 activities is proposed.
authors.affiliation: Institute of Chemistry of São Carlos, University of São Paulo - USP, São Carlos, SP 13560-970, Brazil.
authors.forename: Thiago V
authors.initials: TV
authors.lastname: Seraphim
authors.affiliation: Department of Genetics and Evolution, Federal University of São Carlos - UFSCar, São Carlos, SP 13565-905, Brazil.
authors.forename: Lisandra M
authors.initials: LM
authors.lastname: Gava
authors.affiliation: Institute of Chemistry, University of Campinas - UNICAMP, P.O. Box 6154, Campinas, SP 13083-970, Brazil.
authors.forename: David Z
authors.initials: DZ
authors.lastname: Mokry
authors.affiliation: Institute of Chemistry, University of Campinas - UNICAMP, P.O. Box 6154, Campinas, SP 13083-970, Brazil; Institute of Biology, University of Campinas - UNICAMP, Campinas, SP 13083-970, Brazil.
authors.forename: Thiago C
authors.initials: TC
authors.lastname: Cagliari
authors.affiliation: Institute of Physics, University of São Paulo - USP, São Paulo, SP 05508-090, Brazil.
authors.forename: Leandro R S
authors.initials: LR
authors.lastname: Barbosa
authors.affiliation: Institute of Chemistry, University of Campinas - UNICAMP, P.O. Box 6154, Campinas, SP 13083-970, Brazil. Electronic address: cramos@iqm.unicamp.br.
authors.forename: Carlos H I
authors.initials: CH
authors.lastname: Ramos
authors.affiliation: Institute of Chemistry of São Carlos, University of São Paulo - USP, São Carlos, SP 13560-970, Brazil. Electronic address: borgesjc@iqsc.usp.br.
authors.forename: Júlio C
authors.initials: JC
authors.lastname: Borges
mesh_terms: D006358:Hot Temperature; D006801:Humans; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D018832:Molecular Chaperones
keywords: Hsp90; Molecular chaperone; Sba1; p19; p23