Koh Young Hoon, Kim So-Jung, Roh Soung-Hun
School of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, South Korea.
FEBS Lett. 2025 Feb;599(4):512-529. doi: 10.1002/1873-3468.15059. Epub 2024 Nov 28.
Nanodiscs, consisting of a lipid bilayer surrounded by membrane scaffold proteins (MSPs), are extensively used to study membrane proteins (MPs) because they provide a stable lipid environment. However, the precise mechanism governing MP behavior within the nanodisc remains elusive. Here, we examined the cryo-EM structures of various MPs reconstituted in nanodiscs from EMPIAR. By analyzing the heterogeneity and interactions in the nanodiscs, we discovered that MPs display a distinct spatial preference toward the edges of the nanodisc shells. Furthermore, MPs can establish direct, amphipathic interactions with the MSPs, causing a reduction in local protein dynamics. These interactions may rearrange MSP-MSP interactions into MP-MSP interactions. Collectively, we provide structural insights into how nanodiscs contribute to MP structural behavior and dynamics. Impact statement Nanodiscs are used to study membrane proteins (MPs), but the mechanisms governing the behavior of MPs within nanodiscs remain elusive. Here, we provide structural insights into how nanodiscs contribute to the behavior of MPs, which will aid the interpretation of cryo-EM studies performed using nanodiscs.
纳米盘由被膜支架蛋白（MSP）包围的脂质双层组成，由于能提供稳定的脂质环境，因此被广泛用于研究膜蛋白（MP）。然而，纳米盘内MP行为的精确调控机制仍不清楚。在这里，我们研究了从EMPIAR获得的在纳米盘中重构的各种MP的冷冻电镜结构。通过分析纳米盘中的异质性和相互作用，我们发现MP对纳米盘壳的边缘表现出明显的空间偏好。此外，MP可以与MSP建立直接的两亲性相互作用，导致局部蛋白质动力学降低。这些相互作用可能会将MSP-MSP相互作用重排为MP-MSP相互作用。总体而言，我们提供了关于纳米盘如何影响MP结构行为和动力学的结构见解。影响声明 纳米盘用于研究膜蛋白（MP），但纳米盘内MP行为的调控机制仍不清楚。在这里，我们提供了关于纳米盘如何影响MP行为的结构见解，这将有助于解释使用纳米盘进行的冷冻电镜研究。
