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

07:00 EST 30th November 2019 | BioPortfolio

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

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 C-detected NMR, is especially suitable to address these questions. We applied a C-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.

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This article was published in the following journal.

Name: Journal of molecular biology
ISSN: 1089-8638
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Medical and Biotech [MESH] Definitions

Functional proteins that do not have unique, stable, folded, three-dimensional native structures or that possess non-ordered regions under physiological conditions. They are characterized by extraordinary structural flexibility and plasticity, which enable them to adopt different conformations in response to different stimuli or different interactions.

Protein domains that are enriched in PROLINE. The cyclical nature of proline causes the peptide bonds it forms to have a limited degree of conformational mobility. Therefore the presence of multiple prolines in close proximity to each other can convey a distinct conformational arrangement to a peptide chain.

A family of low molcular-weight proteins that contain PROLINE-RICH PROTEIN DOMAINS. Members of this family play a role in the formation of an insoluble cornified envelope beneath the plasma membrane of stratified squamous epithelial cells.

The first enzyme of the proline degradative pathway. It catalyzes the oxidation of proline to pyrroline-5-carboxylic acid in the presence of oxygen and water. The action is not reversible. The specific activity of proline oxidase increases with age. EC 1.5.3.-.

An approximately 40 amino acid protein domain that occurs in a variety of unrelated proteins and may be repeated up to four times in some proteins. It is characterized by two TRYPTOHAN residues (WW) about 20 amino acids apart and folds into a stable triple-stranded BETA-SHEET. It binds PROLINE-RICH PROTEIN DOMAINS and PHOSPHOSERINE or PHOSPHOTHREONINE-containing protein domains that occur in many signal transducing and cytoskeletal proteins, such as DYSTROPHIN.

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