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Evaluating the Effect of Phosphorylation on the Structure and Dynamics of Hsp27 Dimers by Means of Ion Mobility Mass Spectrometry

Journal Article


Abstract


  • The quaternary structure and dynamics of the human small heat-shock protein Hsp27 are linked to its molecular chaperone function and influenced by post-translational modifications, including phosphorylation. Phosphorylation of Hsp27 promotes oligomer dissociation and can enhance chaperone activity. This study explored the impact of phosphorylation on the quaternary structure and dynamics of Hsp27. Using mutations that mimic phosphorylation, and ion mobility mass spectrometry, we show that successive substitutions result in an increase in the conformational heterogeneity of Hsp27 dimers. In contrast, we did not detect any changes in the structure of an Hsp27 12-mer, representative of larger Hsp27 oligomers. Our data suggest that oligomer dissociation and increased flexibility of the dimer contribute to the enhanced chaperone activity of phosphorylated Hsp27. Thus, post-translational modifications such as phosphorylation play a crucial role in modulating both the tertiary and quaternary structure of Hsp27, which is pivotal to its function as a key component of the proteostasis network in cells. Our data demonstrate the utility of ion mobility mass spectrometry for probing the structure and dynamics of heterogeneous proteins.

Authors


  •   Jovcevski, Blagojce (external author)
  •   Kelly, Megan A.
  •   Aquilina, John Andrew. (external author)
  •   Benesch, Justin (external author)
  •   Ecroyd, Heath

Publication Date


  • 2017

Citation


  • Jovcevski, B., Kelly, M. A., Aquilina, J., Benesch, J. L. P. & Ecroyd, H. (2017). Evaluating the Effect of Phosphorylation on the Structure and Dynamics of Hsp27 Dimers by Means of Ion Mobility Mass Spectrometry. Analytical Chemistry, 89 (24), 13275-13282.

Scopus Eid


  • 2-s2.0-85038877940

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1195

Number Of Pages


  • 7

Start Page


  • 13275

End Page


  • 13282

Volume


  • 89

Issue


  • 24

Place Of Publication


  • United States

Abstract


  • The quaternary structure and dynamics of the human small heat-shock protein Hsp27 are linked to its molecular chaperone function and influenced by post-translational modifications, including phosphorylation. Phosphorylation of Hsp27 promotes oligomer dissociation and can enhance chaperone activity. This study explored the impact of phosphorylation on the quaternary structure and dynamics of Hsp27. Using mutations that mimic phosphorylation, and ion mobility mass spectrometry, we show that successive substitutions result in an increase in the conformational heterogeneity of Hsp27 dimers. In contrast, we did not detect any changes in the structure of an Hsp27 12-mer, representative of larger Hsp27 oligomers. Our data suggest that oligomer dissociation and increased flexibility of the dimer contribute to the enhanced chaperone activity of phosphorylated Hsp27. Thus, post-translational modifications such as phosphorylation play a crucial role in modulating both the tertiary and quaternary structure of Hsp27, which is pivotal to its function as a key component of the proteostasis network in cells. Our data demonstrate the utility of ion mobility mass spectrometry for probing the structure and dynamics of heterogeneous proteins.

Authors


  •   Jovcevski, Blagojce (external author)
  •   Kelly, Megan A.
  •   Aquilina, John Andrew. (external author)
  •   Benesch, Justin (external author)
  •   Ecroyd, Heath

Publication Date


  • 2017

Citation


  • Jovcevski, B., Kelly, M. A., Aquilina, J., Benesch, J. L. P. & Ecroyd, H. (2017). Evaluating the Effect of Phosphorylation on the Structure and Dynamics of Hsp27 Dimers by Means of Ion Mobility Mass Spectrometry. Analytical Chemistry, 89 (24), 13275-13282.

Scopus Eid


  • 2-s2.0-85038877940

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1195

Number Of Pages


  • 7

Start Page


  • 13275

End Page


  • 13282

Volume


  • 89

Issue


  • 24

Place Of Publication


  • United States