Fluorine NMR study of proline-rich sequences using fluoroprolines.

Autor: Sinnaeve D; Univ. Lille, Inserm, Institut Pasteur de Lille, CHU Lille, U1167 - Risk Factors and Molecular Determinants of Aging-Related Diseases (RID-AGE), 59000 Lille, France.; CNRS, ERL9002 - Integrative Structural Biology, 59000 Lille, France., Ben Bouzayene A; Department of Integrative Structural Biology, IGBMC, University of Strasbourg, Inserm U1258, CNRS UMR 7104, 1 rue Laurent Fries, 67404 Illkirch, France., Ottoy E; Department of Organic and Macromolecular Chemistry, Ghent University, Campus Sterre, S4, Krijgslaan 281, 9000 Ghent, Belgium., Hofman GJ; Department of Organic and Macromolecular Chemistry, Ghent University, Campus Sterre, S4, Krijgslaan 281, 9000 Ghent, Belgium.; School of Chemistry, University of Southampton, Southampton SO17 1BJ, United Kingdom., Erdmann E; Department of Integrative Structural Biology, IGBMC, University of Strasbourg, Inserm U1258, CNRS UMR 7104, 1 rue Laurent Fries, 67404 Illkirch, France., Linclau B; School of Chemistry, University of Southampton, Southampton SO17 1BJ, United Kingdom., Kuprov I; School of Chemistry, University of Southampton, Southampton SO17 1BJ, United Kingdom., Martins JC; Department of Organic and Macromolecular Chemistry, Ghent University, Campus Sterre, S4, Krijgslaan 281, 9000 Ghent, Belgium., Torbeev V; Institut de Science et d'Ingénierie Supramoléculaires (ISIS), International Center for Frontier Research in Chemistry (icFRC), University of Strasbourg, CNRS UMR 7006, 67000 Strasbourg, France., Kieffer B; Department of Integrative Structural Biology, IGBMC, University of Strasbourg, Inserm U1258, CNRS UMR 7104, 1 rue Laurent Fries, 67404 Illkirch, France.
Jazyk: angličtina
Zdroj: Magnetic resonance (Gottingen, Germany) [Magn Reson (Gott)] 2021 Nov 09; Vol. 2 (2), pp. 795-813. Date of Electronic Publication: 2021 Nov 09 (Print Publication: 2021).
DOI: 10.5194/mr-2-795-2021
Abstrakt: Proline homopolymer motifs are found in many proteins; their peculiar conformational and dynamic properties are often directly involved in those proteins' functions. However, the dynamics of proline homopolymers is hard to study by NMR due to a lack of amide protons and small chemical shift dispersion. Exploiting the spectroscopic properties of fluorinated prolines opens interesting perspectives to address these issues. Fluorinated prolines are already widely used in protein structure engineering - they introduce conformational and dynamical biases - but their use as 19 F NMR reporters of proline conformation has not yet been explored. In this work, we look at model peptides where C γ -fluorinated prolines with opposite configurations of the chiral C γ centre have been introduced at two positions in distinct polyproline segments. By looking at the effects of swapping these (4 R )-fluoroproline and (4 S )-fluoroproline within the polyproline segments, we were able to separate the intrinsic conformational properties of the polyproline sequence from the conformational alterations instilled by fluorination. We assess the fluoroproline 19 F relaxation properties, and we exploit the latter in elucidating binding kinetics to the SH3 (Src homology 3) domain.
Competing Interests: The contact author has declared that neither they nor their co-authors have any competing interests.
(Copyright: © 2021 Davy Sinnaeve et al.)
Databáze: MEDLINE
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