title: Binding determinants of the small heat shock protein, αB-crystallin: recognition of the 'IxI' motif.
abstract: Small heat shock proteins (sHSPs) play a central role in protein homeostasis under conditions of stress by binding partly unfolded, aggregate-prone proteins and keeping them soluble. Like many sHSPs, the widely expressed human sHSP, αB-crystallin ('αB'), forms large polydisperse multimeric assemblies. Molecular interactions involved in both sHSP function and oligomer formation remain to be delineated. A growing database of structural information reveals that a central conserved α-crystallin domain (ACD) forms dimeric building blocks, while flanking N- and C-termini direct the formation of larger sHSP oligomers. The most commonly observed inter-subunit interaction involves a highly conserved C-terminal 'IxI/V' motif and a groove in the ACD that is also implicated in client binding. To investigate the inherent properties of this interaction, peptides mimicking the IxI/V motif of αB and other human sHSPs were tested for binding to dimeric αB-ACD. IxI-mimicking peptides bind the isolated ACD at 22°C in a manner similar to interactions observed in the oligomer at low temperature, confirming these interactions are likely to exist in functional αB oligomers.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195-7350, USA.
authors.forename: Scott P
authors.initials: SP
authors.lastname: Delbecq
authors.forename: Stefan
authors.initials: S
authors.lastname: Jehle
authors.forename: Rachel
authors.initials: R
authors.lastname: Klevit
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics / Q000502:physiology*; D050888:Heat-Shock Proteins, Small / Q000378:metabolism*; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization / Q000502:physiology*; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000378:metabolism; D013696:Temperature; D038203:alpha-Crystallin B Chain / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: C059215:CRYAB protein, human; D050888:Heat-Shock Proteins, Small; D010455:Peptides; D021122:Protein Subunits; D038203:alpha-Crystallin B Chain