Reduced Internal Friction by Osmolyte Interaction in Intrinsically Disordered Myelin Basic Protein

Laura R. Stingaciu; Ralf Biehl; Do Changwoo; Dieter Richter; Andreas M. Stadler

doi:10.1021/acs.jpclett.9b03001

Reduced Internal Friction by Osmolyte Interaction in Intrinsically Disordered Myelin Basic Protein

Laura R. Stingaciu, Ralf Biehl, Do Changwoo, Dieter Richter, Andreas M. Stadler

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Urea is a strong denaturing osmolyte that disrupts noncovalent bonds in proteins. Here, we present a small-angle neutron scattering (SANS) and neutron spin-echo spectroscopy (NSE) study on the structure and dynamics of the intrinsically disordered myelin basic protein (MBP) denatured by urea. SANS results show that urea-denatured MBP is more compact than ideal polymers, while its secondary structure content is entirely lost. NSE experiments reveal concomitantly an increase of the relaxation time and of the amplitude of internal motions in urea-denatured MBP as compared to native MBP. If interpreted in terms of the Zimm model including internal friction (ZIF), the internal friction parameter decreased by a factor of 6.5. Urea seems to not only smooth local energy barriers, reducing internal friction on a local scale, but also significantly reduces the overall depth of the global energy landscape. This leads to a nearly complete loss of restoring forces beyond entropic forces and in turn allows for larger motional amplitudes. Obviously, the noncovalent H-bonds are largely eliminated, driving the unfolded protein to be more similar to a synthetic polymer.

Original language	English
Pages (from-to)	292-296
Number of pages	5
Journal	Journal of Physical Chemistry Letters
Volume	11
Issue number	1
DOIs	https://doi.org/10.1021/acs.jpclett.9b03001
State	Published - Jan 2 2020
Externally published	Yes

Funding

Neutron beam time for this research has been allocated by the Jülich Centre for Neutron Sciences through the Scientific User Facilities Division, Office of Basic Energy Sciences, U.S. Department of Energy under IPTS-7788, IPTS-7963, and IPTS-8775. The authors acknowledge the KWS-2 instrument team at FRM2 reactor Garching for help with preliminary SANS measurements not shown here, R. Moody and Dr. K. Weiss for SNS biochemistry lab support, Dr. H.M. O’Neil and Dr. V.G. Vandavasi for help with CD measurements, and Estela Suarez for the TOC graphics.

Funders	Funder number
Jülich Centre for Neutron Sciences
Office of Basic Energy Sciences
U.S. Department of Energy	IPTS-7788, IPTS-7963, IPTS-8775

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10.1021/acs.jpclett.9b03001

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title = "Reduced Internal Friction by Osmolyte Interaction in Intrinsically Disordered Myelin Basic Protein",

abstract = "Urea is a strong denaturing osmolyte that disrupts noncovalent bonds in proteins. Here, we present a small-angle neutron scattering (SANS) and neutron spin-echo spectroscopy (NSE) study on the structure and dynamics of the intrinsically disordered myelin basic protein (MBP) denatured by urea. SANS results show that urea-denatured MBP is more compact than ideal polymers, while its secondary structure content is entirely lost. NSE experiments reveal concomitantly an increase of the relaxation time and of the amplitude of internal motions in urea-denatured MBP as compared to native MBP. If interpreted in terms of the Zimm model including internal friction (ZIF), the internal friction parameter decreased by a factor of 6.5. Urea seems to not only smooth local energy barriers, reducing internal friction on a local scale, but also significantly reduces the overall depth of the global energy landscape. This leads to a nearly complete loss of restoring forces beyond entropic forces and in turn allows for larger motional amplitudes. Obviously, the noncovalent H-bonds are largely eliminated, driving the unfolded protein to be more similar to a synthetic polymer.",

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AU - Changwoo, Do

AU - Richter, Dieter

AU - Stadler, Andreas M.

PY - 2020/1/2

Y1 - 2020/1/2

N2 - Urea is a strong denaturing osmolyte that disrupts noncovalent bonds in proteins. Here, we present a small-angle neutron scattering (SANS) and neutron spin-echo spectroscopy (NSE) study on the structure and dynamics of the intrinsically disordered myelin basic protein (MBP) denatured by urea. SANS results show that urea-denatured MBP is more compact than ideal polymers, while its secondary structure content is entirely lost. NSE experiments reveal concomitantly an increase of the relaxation time and of the amplitude of internal motions in urea-denatured MBP as compared to native MBP. If interpreted in terms of the Zimm model including internal friction (ZIF), the internal friction parameter decreased by a factor of 6.5. Urea seems to not only smooth local energy barriers, reducing internal friction on a local scale, but also significantly reduces the overall depth of the global energy landscape. This leads to a nearly complete loss of restoring forces beyond entropic forces and in turn allows for larger motional amplitudes. Obviously, the noncovalent H-bonds are largely eliminated, driving the unfolded protein to be more similar to a synthetic polymer.

AB - Urea is a strong denaturing osmolyte that disrupts noncovalent bonds in proteins. Here, we present a small-angle neutron scattering (SANS) and neutron spin-echo spectroscopy (NSE) study on the structure and dynamics of the intrinsically disordered myelin basic protein (MBP) denatured by urea. SANS results show that urea-denatured MBP is more compact than ideal polymers, while its secondary structure content is entirely lost. NSE experiments reveal concomitantly an increase of the relaxation time and of the amplitude of internal motions in urea-denatured MBP as compared to native MBP. If interpreted in terms of the Zimm model including internal friction (ZIF), the internal friction parameter decreased by a factor of 6.5. Urea seems to not only smooth local energy barriers, reducing internal friction on a local scale, but also significantly reduces the overall depth of the global energy landscape. This leads to a nearly complete loss of restoring forces beyond entropic forces and in turn allows for larger motional amplitudes. Obviously, the noncovalent H-bonds are largely eliminated, driving the unfolded protein to be more similar to a synthetic polymer.

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Reduced Internal Friction by Osmolyte Interaction in Intrinsically Disordered Myelin Basic Protein

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