Skip to main content
Article thumbnail
Location of Repository

Wrapping the alpha-crystallin domain fold in a chaperone assembly

By R. Stamler, G. Kappé, W.C. Boelens and Christine Slingsby

Abstract

Small heat shock proteins (sHsps) are oligomers that perform a protective function by binding denatured proteins. Although ubiquitous, they are of variable sequence except for a C-terminal similar to 90-residue "alpha-crystallin domain". Unlike larger stress response chaperones, sHsps are ATP-independent and generally form polydisperse assemblies. One proposed mechanism of action involves these assemblies breaking into smaller subunits in response to stress, before binding unfolding substrate and reforming into larger complexes. Two previously solved non-metazoan sHsp multimers are built from dimers formed by domain swapping between the alpha-crystallin domains,. adding to evidence that the smaller subunits are dimers. Here, the 2.5 angstrom resolution structure of an sHsp from the parasitic flatworm Taenia saginata Tsp36, the first metazoan crystal structure, shows a new mode of dimerization involving N-terminal regions, which differs from that seen for non-metazoan sHsps. Sequence differences in the a-crystallin domains between metazoans and nonmetazoans are critical to the different mechanism of dimerization, suggesting that some structural features seen for Tsp36 may be generalized to other metazoan sHsps. The structure also indicates scope for flexible assembly of subunits, supporting the proposed process of oligomer breakdown, substrate binding and reassembly as the chaperone mechanism. It further shows how sHsps can bind coil and secondary structural elements by wrapping them around the alpha-crystallin domain. The structure also illustrates possible roles for conserved residues associated with disease, and suggests a mechanism for the sHsp-related pathogenicity of some flatworm infections. Tsp36, like other flatworm sHsps, possesses two divergent sHsp repeats per monomer. Together with the two previously solved structures, a total of four alpha-crystallin domain structures are now available, giving a better definition of domain boundaries for sHsps

Topics: bcs
Publisher: Elsevier
Year: 2005
OAI identifier: oai:eprints.bbk.ac.uk.oai2:303

Suggested articles

Citations

  1. (2005). A Chaperone Pathway in Protein Disaggregation: Hsp26 alters the nature of protein aggregates to facilitate reactivation by Hsp104. doi
  2. (2005). A dual role for the N-terminal region of Mycobacterium tuberculosis Hsp16.3 in self-oligomerization and binding denaturing substrate proteins. doi
  3. (1997). A small heat shock protein stably binds heat-denatured model substrates and can maintain a substrate in a folding-competent state. doi
  4. (2002). Actin cytoskeleton and small heat shock proteins: how do they interact? doi
  5. (1992). Alpha-crystallin can function as a molecular chaperone. doi
  6. (2003). Analysis of cDNAs coding for immunologically dominant antigens from an oncosphere-specific cDNA library of Echinococcus multilocularis. doi
  7. (2004). Analysis of the regulation of the molecular chaperone Hsp26 by temperatureinduced dissociation: the N-terminal domail is important for oligomer assembly and the binding of unfolding proteins. doi
  8. (2004). Association of the chaperone alphaB-crystallin with titin in heart muscle. doi
  9. (1997). Binding of nonnative protein to Hsp25 during heat shock creates a reservoir of folding intermediates for reactivation. doi
  10. (2000). Chaperone activity and homo- and heterooligomer formation of bacterial small heat shock proteins. doi
  11. (2004). Chaperone activity of cytosolic small heat shock proteins from wheat. doi
  12. (2001). Crystal structure and assembly of a eukaryotic small heat shock protein.
  13. (1998). Crystal structure of a small heatshock protein.
  14. (1998). Crystallography and NMR system (CNS): A new software system for macromolecular structure determination. Acta Cryst. doi
  15. (2004). Desmin aggregate formation by R120G alphaB-crystallin is caused by altered filament interactions and is dependent upon network status in cells. doi
  16. (2004). Essential role of the NH2-terminal WD/EPF motif in the phosphorylation-activated protective function of mammalian Hsp27. doi
  17. (2002). Functional similarities between the small heat shock proteins Mycobacterium tuberculosis HSP 16.3 and human alphaB-crystallin. doi
  18. (1998). Genealogy of the alpha-crystallin - small heat-shock protein superfamily. doi
  19. (2004). Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy. doi
  20. (2000). HSP25, a small heat shock protein associated with dense bodies and M-lines of body wall muscle in Caenorhabditis elegans. doi
  21. (1999). Hsp26: a temperature-regulated chaperone. doi
  22. (2004). HSP27 but not HSP70 has a potent protective effect against alpha-synuclein-induced cell death in mammalian neuronal cells. doi
  23. (2003). human genome encodes 10 alpha-crystallin-related small heat shock proteins: HspB1-10. Cell Stress Chaperones, doi
  24. (1998). Identification of the immunodominant T cell epitope of p38, a major egg antigen, and characterization of the epitopespecific Th responsiveness during murine schistosomiasis mansoni.
  25. (2004). Interaction of the molecular chaperone alphaB-crystallin with alpha-synuclein: effects on amyloid fibril formation and chaperone activity. doi
  26. (1997). Maximum-likelihood Heavy Atom Parameter Refinement for Multiple Isomorphous Replacement and Multiwavelength Anomalous Diffraction Methods. Methods Enzymol. doi
  27. (2000). Mouse Hsp25, a small shock protein. The role of its C-terminal extension in oligomerization and chaperone action. doi
  28. (2004). Mutants in a small heat shock protein that affect the oligomeric state - Analysis and allele-specific suppression. doi
  29. (2003). On the mechanism of chaperone activity of the small heat-shock protein of Methanococcus jannaschii. doi
  30. (1978). On the treatment of negative intensity observations. Acta Cryst. doi
  31. (1997). Preparation of selenomethionyl proteins for phase determination. doi
  32. (1993). PROCHECK: a program to check the stereochemical quality of protein structures. doi
  33. (2000). Rapid automatic detection and alignment of repeats in protein sequences. doi
  34. (1992). Recent changes to the MOSFLM package for processing film and image plate data.
  35. (2003). Refolding of substrates bound to small Hsps relies on a disaggregation reaction mediated most efficiently by ClpB/DnaK. doi
  36. (2003). Regulation of aging and agerelated disease by DAF-16 and heat-shock factor. doi
  37. (1986). Sequence and expression of a major egg antigen from Schistosoma mansoni. Homologies to heat shock proteins and alpha-crystallins. doi
  38. (1998). Sequence and preliminary characterisation of a Taenia saginata oncosphere gene homologue of the small heat-shock protein family. doi
  39. (2004). Shocking degeneration. doi
  40. (2000). Small heat shock proteins, the cytoskeleton, and inclusion body formation. doi
  41. (2000). Structure and function of small heat shock/alphacrystallin proteins: established concepts and emerging ideas. doi
  42. (2001). Structure and function of the small heat shock protein/alpha-crystallin family of molecular chaperones. doi
  43. (2002). Subunit exchange of multimeric protein complexes. Real-time monitoring of subunit exchange between small heat shock proteins by using electrospray mass spectrometry. doi
  44. (2000). Subunit exchange of small heat shock proteins. Analysis of oligomer formation of alphaAcrystallin and Hsp27 by fluorescence resonance energy transfer and sitedirected truncations. doi
  45. (2004). The identity of proteins associated with a small heat shock protein during heat stress in vivo indicates that these chaperones protect a wide range of cellular functions. doi
  46. (2001). The relationship between alphaB-crystallin and neurofibrillary tangles in Alzheimer's disease. doi
  47. (2004). Tsp36, a tapeworm small heat-shock protein with a duplicated alpha-crystallin domain, forms dimers and tetramers with good chaperone-like activity. doi
  48. (1999). XtalView/Xfit - A Versatile Program for Manipulating Atomic Coordinates and Electron Density. doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.