title: The functional roles of the unstructured N- and C-terminal regions in αB-crystallin and other mammalian small heat-shock proteins.
abstract: Small heat-shock proteins (sHsps), such as αB-crystallin, are one of the major classes of molecular chaperone proteins. In vivo, under conditions of cellular stress, sHsps are the principal defence proteins that prevent large-scale protein aggregation. Progress in determining the structure of sHsps has been significant recently, particularly in relation to the conserved, central and β-sheet structured α-crystallin domain (ACD). However, an understanding of the structure and functional roles of the N- and C-terminal flanking regions has proved elusive mainly because of their unstructured and dynamic nature. In this paper, we propose functional roles for both flanking regions, based around three properties: (i) they act in a localised crowding manner to regulate interactions with target proteins during chaperone action, (ii) they protect the ACD from deleterious amyloid fibril formation and (iii) the flexibility of these regions, particularly at the extreme C-terminus in mammalian sHsps, provides solubility for sHsps under chaperone and non-chaperone conditions. In the eye lens, these properties are highly relevant as the crystallin proteins, in particular the two sHsps αA- and αB-crystallin, are present at very high concentrations.
authors.affiliation: Research School of Chemistry, The Australian National University, Acton, ACT, 2601, Australia. john.carver@anu.edu.au.
authors.forename: John A
authors.initials: JA
authors.lastname: Carver
authors.affiliation: Research School of Chemistry, The Australian National University, Acton, ACT, 2601, Australia.
authors.forename: Aidan B
authors.initials: AB
authors.lastname: Grosas
authors.affiliation: School of Biological Sciences and the Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, 2522, Australia.
authors.forename: Heath
authors.initials: H
authors.lastname: Ecroyd
authors.affiliation: Department of Biosciences, Durham University, Durham, DH1 3LE, UK.
authors.forename: Roy A
authors.initials: RA
authors.lastname: Quinlan
mesh_terms: D000818:Animals; D050888:Heat-Shock Proteins, Small / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D066329:Protein Aggregates; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D060066:Protein Interaction Maps; D055503:Protein Multimerization; D038203:alpha-Crystallin B Chain / Q000737:chemistry* / Q000378:metabolism
chemical_list: D050888:Heat-Shock Proteins, Small; D066329:Protein Aggregates; D038203:alpha-Crystallin B Chain
keywords: AlphaB-crystallin; Function; Molecular chaperone; Small heat-shock proteins; Structure; Unstructured regions