title: The N-terminal helix controls the transition between the soluble and amyloid states of an FF domain.
abstract: BACKGROUND
  Protein aggregation is linked to the onset of an increasing number of human nonneuropathic (either localized or systemic) and neurodegenerative disorders. In particular, misfolding of native α-helical structures and their self-assembly into nonnative intermolecular β-sheets has been proposed to trigger amyloid fibril formation in Alzheimer's and Parkinson's diseases.
  
  
  METHODS
  Here, we use a battery of biophysical techniques to elucidate the conformational conversion of native α-helices into amyloid fibrils using an all-α FF domain as a model system.
  
  
  RESULTS
  We show that under mild denaturing conditions at low pH this FF domain self-assembles into amyloid fibrils. Theoretical and experimental dissection of the secondary structure elements in this domain indicates that the helix 1 at the N-terminus has both the highest α-helical and amyloid propensities, controlling the transition between soluble and aggregated states of the protein.
  
  
  CONCLUSIONS
  The data illustrates the overlap between the propensity to form native α-helices and amyloid structures in protein segments.
  
  
  CONCLUSIONS
  The results presented contribute to explain why proteins cannot avoid the presence of aggregation-prone regions and indeed use stable α-helices as a strategy to neutralize such potentially deleterious stretches.
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Castillo
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Chiti
authors.forename: Salvador
authors.initials: S
authors.lastname: Ventura
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry; D005656:Fungal Proteins / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D017433:Protein Structure, Secondary; D059748:Proteolysis; D012995:Solubility; D013816:Thermodynamics
chemical_list: D000682:Amyloid; D002352:Carrier Proteins; D005656:Fungal Proteins; D010455:Peptides