title: Association between foldability and aggregation propensity in small disulfide-rich proteins.
abstract: OBJECTIVE
  Disulfide-rich domains (DRDs) are small proteins whose native structure is stabilized by the presence of covalent disulfide bonds. These domains are versatile and can perform a wide range of functions. Many of these domains readily unfold on disulfide bond reduction, suggesting that in the absence of covalent bonding they might display significant disorder.
  
  
  RESULTS
  Here, we analyzed the degree of disorder in 97 domains representative of the different DRDs families and demonstrate that, in terms of sequence, many of them can be classified as intrinsically disordered proteins (IDPs) or contain predicted disordered regions. The analysis of the aggregation propensity of these domains indicates that, similar to IDPs, their sequences are more soluble and have less aggregating regions than those of other globular domains, suggesting that they might have evolved to avoid aggregation after protein synthesis and before they can attain its compact and covalently linked native structure.
  
  
  CONCLUSIONS
  DRDs, which resemble IDPs in the reduced state and become globular when their disulfide bonds are formed, illustrate the link between protein folding and aggregation propensities and how these two properties cannot be easily dissociated, determining the main traits of the folding routes followed by these small proteins to attain their native oxidized states.
authors.affiliation: Departament de Bioquimica i Biologia Molecular, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona , Barcelona, Spain .
authors.forename: Hugo
authors.initials: H
authors.lastname: Fraga
authors.forename: Ricardo
authors.initials: R
authors.lastname: Graña-Montes
authors.forename: Ricard
authors.initials: R
authors.lastname: Illa
authors.forename: Giovanni
authors.initials: G
authors.lastname: Covaleda
authors.forename: Salvador
authors.initials: S
authors.lastname: Ventura
mesh_terms: D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D066329:Protein Aggregates; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary
chemical_list: D004220:Disulfides; D066329:Protein Aggregates