Intramolecular Diffusion in α-Synuclein: It Depends on How You Measure It

Jaie Woodard, Kinshuk R. Srivastava, Gil Rahamim, Asaf Grupi, Steven Hogan, David J. Witalka, Grzegorz Nawrocki, Elisha Haas, Michael Feig, Lisa J. Lapidus

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Intramolecular protein diffusion, the motion of one part of the polypeptide chain relative to another part, is a fundamental aspect of protein folding and may modulate amyloidogenesis of disease-associated intrinsically disordered proteins. Much work has determined such diffusion coefficients using a variety of probes, but there has been an apparent discrepancy between measurements using long-range probes, such as fluorescence resonance energy transfer, and short-range probes, such as Trp-Cys quenching. In this work, we make both such measurements on the same protein, α-synuclein, and confirm that such discrepancy exists. Molecular dynamics simulations suggest that such differences result from a diffusion coefficient that depends on the spatial distance between probes. Diffusional estimates in good quantitative agreement with experiment are obtained by accounting for the distinct distance ranges probed by fluorescence resonance energy transfer and Trp-Cys quenching.

Original languageEnglish
Pages (from-to)1190-1199
Number of pages10
JournalBiophysical Journal
Volume115
Issue number7
DOIs
StatePublished - 2 Oct 2018

Bibliographical note

Funding Information:
Funding support from National Science Foundation MCB 1330560 (to M.F., J.W., and G.N.), National Institutes of Health R01 GM100908 (to K.R.S., S.H., D.J.W., and L.J.L.), and National Institutes of Health R35 GM126948 (to M.F.) is acknowledged.

Funding Information:
Funding support from National Science Foundation MCB 1330560 (to M.F., J.W., and G.N.), National Institutes of Health R01 GM100908 (to K.R.S., S.H., D.J.W., and L.J.L.), and National Institutes of Health R35 GM126948 (to M.F.) is acknowledged.

Publisher Copyright:
© 2018 Biophysical Society

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