Binding determinants of the small heat shock protein, αB-crystallin: recognition of the 'IxI' motif

EMBO J. 2012 Dec 12;31(24):4587-94. doi: 10.1038/emboj.2012.318. Epub 2012 Nov 27.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Motifs / genetics
  • Amino Acid Motifs / physiology*
  • Heat-Shock Proteins, Small / metabolism*
  • Humans
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides / genetics
  • Peptides / metabolism*
  • Protein Binding
  • Protein Multimerization / physiology*
  • Protein Structure, Tertiary
  • Protein Subunits / metabolism
  • Temperature
  • alpha-Crystallin B Chain / isolation & purification
  • alpha-Crystallin B Chain / metabolism*


  • CRYAB protein, human
  • Heat-Shock Proteins, Small
  • Peptides
  • Protein Subunits
  • alpha-Crystallin B Chain