Phosphorylation Increases Persistence Length and End-to-End Distance of a Segment of Tau Protein

Biophysical Journal
Alexander F ChinVincent J Hilser

Abstract

Intrinsically disordered regions of proteins, which lack unique tertiary structure under physiological conditions, are enriched in phosphorylation sites and in significant local bias toward the polyproline II conformation. The overrepresented coincidence of this posttranslational regulatory signal and local conformational bias within unstructured regions raises a question: can phosphorylation serve to manipulate the conformational preferences of a disordered protein? In this study, we use time-resolved fluorescence resonance energy transfer and a, to our knowledge, novel data analysis method to directly measure the end-to-end distance distribution of a phosphorylatable peptide derived from the human microtubule associated protein tau. Our results show that phosphorylation at threonine or serine extends the end-to-end distance and increases the effective persistence length of the tested model peptides. Unexpectedly, the extension is independent of salt concentration, suggestive of a nonelectrostatic origin. The phosphorylation extension and stiffening effect provides a peptide-scale physical interpretation for the posttranslational regulation of the highly abundant protein-protein interactions found in disordered proteins, as we...Continue Reading

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Citations

Aug 27, 2016·Journal of Biomolecular Structure & Dynamics·Alexei A AdzhubeiAlexander A Makarov
Oct 4, 2016·Journal of the American Chemical Society·Srivastav RanganathanRanjith Padinhateeri
Feb 13, 2019·The Journal of Biological Chemistry·Carol J HusebyJeff Kuret
Sep 10, 2020·Proceedings of the National Academy of Sciences of the United States of America·Min-Hyung ChoVincent J Hilser
Apr 2, 2018·The Journal of Chemical Physics·Taylor Firman, Kingshuk Ghosh
Dec 19, 2018·Journal of Molecular Biology·Ranajeet Ghose
Mar 30, 2021·The Journal of Physical Chemistry. B·Zhongmin Zhang, Kateri H DuBay
Jul 24, 2021·Biochimica Et Biophysica Acta. Proteins and Proteomics·Harshita Rastogi, Pramit K Chowdhury
Jul 13, 2021·The Journal of Physical Chemistry. B·Beata Szała-Mendyk, Andrzej Molski
Jan 11, 2018·Chemical Reviews·Huan-Xiang Zhou, Xiaodong Pang

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