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Amyloid fibril formation by circularly permuted and C-terminally deleted mutants.
Corrêa, Daniel H A; Ramos, Carlos H I.
Afiliação
  • Corrêa DH; Institute of Chemistry, University of Campinas-UNICAMP, PO Box 6154, 13083-970 Campinas, SP, Brazil.
Int J Biol Macromol ; 48(4): 583-8, 2011 May 01.
Article em En | MEDLINE | ID: mdl-21300089
The natural N- and C-termini, i.e., the given order of secondary structure segments, are critical for protein folding and stability, as shown by several studies using circularly permuted proteins, mutants that have their N- and C-termini linked and are then digested at another site to create new termini. A previous work showed that circularly permuted mutants of sperm whale myoglobin (Mb) are functional, have native-like folding and bind heme, but are less stable than the wild-type protein and aggregate. The ability of wild-type myoglobin to form amyloid fibrils has been established recently, and because circularly permuted mutations are destabilizing, we asked whether these permutations would also affect the rate of amyloid fibril formation. Our investigations revealed that, indeed, the circularly permuted mutants formed cytotoxic fibrils at a rate higher than that of the wild-type. To further investigate the role of the C-terminus in the overall stability of the protein, we investigated two C-terminally deleted mutant, Mb(1-123) and Mb(1-99), and found that Mb(1-123) formed cytotoxic fibrils at a higher rate than that of the wild-type while Mb(1-99) formed cytotoxic fibrils at a similar rate than that of the wild-type. Collectively, our findings show that the native position of both the N-and C-termini is important for the precise structural architecture of myoglobin.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dobramento de Proteína / Amiloide / Mutação / Mioglobina Idioma: En Revista: Int J Biol Macromol Ano de publicação: 2011 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dobramento de Proteína / Amiloide / Mutação / Mioglobina Idioma: En Revista: Int J Biol Macromol Ano de publicação: 2011 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda