Intrinsically disordered proteins (IDPs) carry out many biological functions. They lack a stable three-dimensional structure, but rather adopt many different conformations in dynamic equilibrium. The interplay between local dynamics and global rearrangements is key for their function. In IDPs, proline residues are significantly enriched. Given their unique physicochemical and structural properties, a more detailed understanding of their potential role in stabilizing partially folded states in IDPs is highly desirable. Nuclear magnetic resonance (NMR) spectroscopy, and in particular 13C-detected NMR, is especially suitable to address these questions. We applied a 13C-detected strategy to study Osteopontin, a largely disordered IDP with a central compact region. By employing the exquisite sensitivity and spectral resolution of these novel techniques we gained unprecedented insight into cis-Pro populations, their local structural dynamics and their role in mediating long-range contacts. Our findings clearly call for a reassessment of the structural and functional role of proline residues in IDPs. The emerging picture shows that proline residues have ambivalent structural roles. They are not simply disorder promoters but rather can, depending on the primary sequence context, act as nucleation sites for structural compaction in IDPs. These unexpected features provide a versatile mechanistic toolbox to enrich the conformational ensembles of IDPs with specific features for adapting to changing molecular and cellular environments.

The ambivalent role of proline residues in an intrinsically disordered protein: from disorder promoters to compaction facilitators / Mateos, Borja; Conrad-Billroth, Clara; Schiavina, Marco; Beier, Andreas; Kontaxis, Georg; Konrat, Robert; Felli, Isabella C.; Pierattelli, Roberta. - In: JOURNAL OF MOLECULAR BIOLOGY. - ISSN 0022-2836. - STAMPA. - 432:(2020), pp. 3093-3111. [10.1016/j.jmb.2019.11.015]

The ambivalent role of proline residues in an intrinsically disordered protein: from disorder promoters to compaction facilitators

Schiavina, Marco;Felli, Isabella C.
;
Pierattelli, Roberta
2020

Abstract

Intrinsically disordered proteins (IDPs) carry out many biological functions. They lack a stable three-dimensional structure, but rather adopt many different conformations in dynamic equilibrium. The interplay between local dynamics and global rearrangements is key for their function. In IDPs, proline residues are significantly enriched. Given their unique physicochemical and structural properties, a more detailed understanding of their potential role in stabilizing partially folded states in IDPs is highly desirable. Nuclear magnetic resonance (NMR) spectroscopy, and in particular 13C-detected NMR, is especially suitable to address these questions. We applied a 13C-detected strategy to study Osteopontin, a largely disordered IDP with a central compact region. By employing the exquisite sensitivity and spectral resolution of these novel techniques we gained unprecedented insight into cis-Pro populations, their local structural dynamics and their role in mediating long-range contacts. Our findings clearly call for a reassessment of the structural and functional role of proline residues in IDPs. The emerging picture shows that proline residues have ambivalent structural roles. They are not simply disorder promoters but rather can, depending on the primary sequence context, act as nucleation sites for structural compaction in IDPs. These unexpected features provide a versatile mechanistic toolbox to enrich the conformational ensembles of IDPs with specific features for adapting to changing molecular and cellular environments.
432
3093
3111
Mateos, Borja; Conrad-Billroth, Clara; Schiavina, Marco; Beier, Andreas; Kontaxis, Georg; Konrat, Robert; Felli, Isabella C.; Pierattelli, Roberta
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1179700
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