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所属单位：航空学院

发表刊物：BIOPHYSICAL JOURNAL

关键字：COARSE-GRAINED MODEL DETERGENT-FREE ISOLATION MEMBRANE-PROTEINS DYNAMICS SIMULATIONS FUNCTIONAL RECONSTITUTION BILAYER NANODISCS VERSATILE TOOL PORE FORMATION FORCE-FIELD ALL-ATOM

摘要：Experimental characterization of membrane proteins often requires solubilization. A recent approach is to use styrene-maleic acid (SMA) copolymers to isolate membrane proteins in nanometer-sized membrane disks, or so-called SMA lipid particles (SMALPs). The approach has the advantage of allowing direct extraction of proteins, keeping their native lipid environment. Despite the growing popularity of using SMALPs, the molecular mechanism behind the process remains poorly understood. Here, we unravel the molecular details of the nanodisk formation by using coarse-grained molecular dynamics simulations. We show how SMA copolymers bind to the lipid bilayer interface, driven by the hydrophobic effect. Due to the concerted action of multiple adsorbed copolymers, large membrane defects appear, including small, water-filled pores. The copolymers can stabilize the rim of these pores, leading to pore growth and membrane disruption. Although complete solubilization is not seen on the timescale of our simulations, self-assembly experiments show that small nanodisks are the thermodynamically preferred end state. Our findings shed light on the mechanism of SMALP formation and on their molecular structure. This can be an important step toward the design of optimized extraction tools for membrane protein research.

ISSN号：0006-3495

是否译文：否

发表时间：2018-08-07

合写作者：Xue, Minmin,Cheng, Lisheng,Faustino, Ignacio,Marrink, Siewert J.

通讯作者：郭万林