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Phosphomimics destabilize Hsp27 oligomeric assemblies and enhance chaperone activity

Journal Article


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Abstract


  • Serine phosphorylation of the mammalian small heat-shock protein Hsp27 at residues 15, 78, and 82 is thought to regulate its structure and chaperone function; however, the site-specific impact has not been established. We used mass spectrometry to assess the combinatorial effect of mutations that mimic phosphorylation upon the oligomeric state of Hsp27. Comprehensive dimerization yielded a relatively uncrowded spectrum, composed solely of even-sized oligomers. Modification at one or two serines decreased the average oligomeric size, while the triple mutant was predominantly a dimer. These changes were reflected in a greater propensity for oligomers to dissociate upon increased modification. The ability of Hsp27 to prevent amorphous or fibrillar aggregation of target proteins was enhanced and correlated with the amount of dissociated species present. We propose that, in vivo, phosphorylation promotes oligomer dissociation, thereby enhancing chaperone activity. Our data support a model in which dimers are the chaperone-active component of Hsp27.

Authors


  •   Jovcevski, Blagojce (external author)
  •   Kelly, Megan A.
  •   Rote, Anthea (external author)
  •   Berg, Tracey
  •   Gastall, Heidi Y. (external author)
  •   Benesch, Justin (external author)
  •   Aquilina, John Andrew. (external author)
  •   Ecroyd, Heath

Publication Date


  • 2015

Citation


  • Jovcevski, B., Kelly, M. A., Rote, A. P., Berg, T., Gastall, H. Y., Benesch, J. L. P., Aquilina, J. Andrew. & Ecroyd, H. (2015). Phosphomimics destabilize Hsp27 oligomeric assemblies and enhance chaperone activity. Chemistry and Biology, 22 (2), 186-195.

Scopus Eid


  • 2-s2.0-84923126434

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3742&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2721

Number Of Pages


  • 9

Start Page


  • 186

End Page


  • 195

Volume


  • 22

Issue


  • 2

Abstract


  • Serine phosphorylation of the mammalian small heat-shock protein Hsp27 at residues 15, 78, and 82 is thought to regulate its structure and chaperone function; however, the site-specific impact has not been established. We used mass spectrometry to assess the combinatorial effect of mutations that mimic phosphorylation upon the oligomeric state of Hsp27. Comprehensive dimerization yielded a relatively uncrowded spectrum, composed solely of even-sized oligomers. Modification at one or two serines decreased the average oligomeric size, while the triple mutant was predominantly a dimer. These changes were reflected in a greater propensity for oligomers to dissociate upon increased modification. The ability of Hsp27 to prevent amorphous or fibrillar aggregation of target proteins was enhanced and correlated with the amount of dissociated species present. We propose that, in vivo, phosphorylation promotes oligomer dissociation, thereby enhancing chaperone activity. Our data support a model in which dimers are the chaperone-active component of Hsp27.

Authors


  •   Jovcevski, Blagojce (external author)
  •   Kelly, Megan A.
  •   Rote, Anthea (external author)
  •   Berg, Tracey
  •   Gastall, Heidi Y. (external author)
  •   Benesch, Justin (external author)
  •   Aquilina, John Andrew. (external author)
  •   Ecroyd, Heath

Publication Date


  • 2015

Citation


  • Jovcevski, B., Kelly, M. A., Rote, A. P., Berg, T., Gastall, H. Y., Benesch, J. L. P., Aquilina, J. Andrew. & Ecroyd, H. (2015). Phosphomimics destabilize Hsp27 oligomeric assemblies and enhance chaperone activity. Chemistry and Biology, 22 (2), 186-195.

Scopus Eid


  • 2-s2.0-84923126434

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3742&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2721

Number Of Pages


  • 9

Start Page


  • 186

End Page


  • 195

Volume


  • 22

Issue


  • 2