Fibril elongation mechanisms of HET-s prion-forming domain: topological evidence for growth polarity.
Proteins
; 79(11): 3067-81, 2011 Nov.
Article
em En
| MEDLINE
| ID: mdl-21989930
ABSTRACT
The prion-forming C-terminal domain of the fungal prion HET-s forms infectious amyloid fibrils at physiological pH. The conformational switch from the nonprion soluble form to the prion fibrillar form is believed to have a functional role, as HET-s in its prion form participates in a recognition process of different fungal strains. On the basis of the knowledge of the high-resolution structure of the prion forming domain HET-s(218-289) in its fibrillar form, we here present a numerical simulation of the fibril growth process, which emphasizes the role of the topological properties of the fibrillar structure. An accurate thermodynamic analysis of the way an intervening HET-s chain is recruited to the tip of the growing fibril suggests that elongation proceeds through a dock and lock mechanism. First, the chain docks onto the fibril by forming the longest ß-strands. Then, the re-arrangement in the fibrillar form of all the rest of the molecule takes place. Interestingly, we also predict that one side of the HET-s fibril is more suitable for sustaining its growth with respect to the other. The resulting strong polarity of fibril growth is a consequence of the complex topology of HET-s fibrillar structure, as the central loop of the intervening chain plays a crucially different role in favoring or not the attachment of the C-terminus tail to the fibril, depending on the growth side.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Príons
/
Proteínas Fúngicas
/
Amiloide
Tipo de estudo:
Health_economic_evaluation
/
Prognostic_studies
Idioma:
En
Revista:
Proteins
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Itália