Home
Resources
Publications
Cholesteryl Hemisuccinate Is Not a Good Replacement for Cholesterol in Lipid Nanodiscs

Cholesteryl Hemisuccinate Is Not a Good Replacement for Cholesterol in Lipid Nanodiscs

Bozena Augustyn, Piotr Stepien, Chetan Poojari, Edouard Mobarak, Agnieszka Polit, Anna Wisniewska-Becker, Tomasz Róg

J Phys Chem B. 2019 Nov 21;123(46):9839-9845.

PMID: 31674185

Abstract:

Nanodiscs are suitable tools for studies of membrane proteins (MPs) due to their ability to mimic native biological membranes, and several MP structures are solved in nanodiscs. Among the various cell membrane components, cholesterol (CHL) is known to regulate protein function and its concentration can reach up to 50 mol %. However, studies comprising cholesterol are challenging due to its hydrophobic nature, hence, nanodiscs with only a low cholesterol concentration have been studied. To overcome the problem, cholesterol analogs with high solubility in polar solutions are often used, and one of them is cholesteryl hemisuccinate (CHS). Nevertheless, in molecular dynamics (MD) simulation, this is not an obstacle. In this study, we performed MD simulations of nanodiscs containing neutral phosphatidylcholine (POPC) lipids, negatively charged phosphatidylglycerol (POPG) lipids, CHL, or negatively charged cholesterol analog, CHS. Our simulations show that CHS increases the order of lipids in nanodiscs; the effect is, however, weaker than CHL and even smaller in nanodiscs. Furthermore, CHS gathered around scaffold proteins while cholesterol was uniformly distributed in the nanodiscs. Thus, nanodiscs with CHS are heterogeneous and not equivalent to nanodiscs with CHL. Finally, we also observed the increased concentration of POPG near the scaffold proteins, driven by electrostatic interactions. The MD results are experimentally validated using electron paramagnetic resonance spectroscopy. These results show that nanodiscs are, in fact, complex structures not easily comparable with planar lipid bilayers.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1510210	Cholesteryl hemisuccinate		1510-21-0	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: