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primary topic: Early folding events protect aggregation-prone regions of a β-rich protein.

Early folding events protect aggregation-prone regions of a β-rich protein.
type: AcademicArticle
type: Article
abstract: Protein folding and aggregation inevitably compete with one another. This competition is even keener for proteins with frustrated landscapes, such as those rich in β structure. It is interesting that, despite their rugged energy landscapes and high β sheet content, intracellular lipid-binding proteins (iLBPs) appear to successfully avoid aggregation, as they are not implicated in aggregation diseases. In this study, we used a canonical iLBP, cellular retinoic acid-binding protein 1 (CRABP1), to understand better how folding is favored over aggregation. Analysis of folding kinetics of point mutants reveals that the folding pathway of CRABP1 involves early barrel closure. This folding mechanism protects sequences in CRABP1 that comprise cores of aggregates as identified by nuclear magnetic resonance. The amino acid conservation pattern in other iLBPs suggests that early barrel closure may be a general strategy for successful folding and minimization of aggregation. We suggest that folding mechanisms in general may incorporate steps that disfavor aggregation.
date: 2013-03-05
volume: 21
issue: 3
is part of: Structure (London, England : 1993)
status: peerReviewed
status: published
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository
subject: QR Microbiology

Cell Press/Science Direct
type: Organization

Structure (London, England : 1993)
type: Collection
issn: 18784186

Beena Krishnan
type: Person
given name: Beena
family name: Krishnan

Lila M Gierasch
type: Person
given name: Lila M
family name: Gierasch

Anastasia Zhuravleva
type: Person
given name: Anastasia
family name: Zhuravleva

Mylene C Ferrolino
type: Person
given name: Mylene C
family name: Ferrolino

Anna M Marcelino-Cruz
type: Person
given name: Anna M
family name: Marcelino-Cruz

Ivan L Budyak
type: Person
given name: Ivan L
family name: Budyak

HTML Summary of #2433 Early folding events protect aggregation-prone regions of a β-rich protein.
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primary topic: Early folding events protect aggregation-prone regions of a β-rich protein.

QR Microbiology
type: Concept