Proline isomerization in the C-terminal region of HSP27

Journal article

In mammals, small heat-shock proteins (sHSPs) typically assemble into interconverting, polydisperse oligomers. The dynamic exchange of sHSP oligomers is regulated, at least in part, by molecular interactions between the α-crystallin domain and the C-terminal region (CTR). Here we report solution-state nuclear magnetic resonance (NMR) spectroscopy investigations of the conformation and dynamics of the disordered and flexible CTR of human HSP27, a systemically expressed sHSP. We observed multiple NMR signals for residues in the vicinity of proline 194, and we determined that, while all observed forms are highly disordered, the extra resonances arise from cis-trans peptidyl-prolyl isomerization about the G193-P194 peptide bond. The cis-P194 state is populated to near 15% at physiological temperatures, and, although both cis- and trans-P194 forms of the CTR are flexible and dynamic, both states show a residual but differing tendency to adopt β-strand conformations. In NMR spectra of an isolated CTR peptide, we observed similar evidence for isomerization involving proline 182, found within the IPI/V motif. Collectively, these data indicate a potential role for cis-trans proline isomerization in regulating the oligomerization of sHSPs.

Authors: Alderson, T; Benesch, J; Baldwin, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Verlag
• Journal: Cell Stress and Chaperones
• Volume: 22
• Issue: 4
• Pages: 639–651
• Publication date: 2017-05-25
• Acceptance date: 2017-03-24
• DOI: 10.1007/s12192-017-0791-z
• EISSN: 1466-1268
• ISSN: 1355-8145
• Language: English
• Keywords: Small heat-shock proteins; Intrinsically disordered proteins; Molecular chaperones; cis-trans proline isomerization; Nuclear magnetic resonance spectroscopy