Derganc Jure, Čopič Alenka
Institute of Biophysics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
Institut Jacques Monod, CNRS, UMR 7592, University Paris Diderot, Sorbonne Paris Cité, F-75013 Paris, France.
Biochim Biophys Acta. 2016 Jun;1858(6):1152-9. doi: 10.1016/j.bbamem.2016.03.009. Epub 2016 Mar 8.
Crowding of asymmetrically-distributed membrane proteins has been recently recognized as an important factor in remodeling of biological membranes, for example during transport vesicle formation. In this paper, we theoretically analyze the effect of protein crowding on membrane bending and examine its dependence on protein size, shape, transmembrane asymmetry and lateral confinement. We consider three scenarios of protein lateral organization, which are highly relevant for cellular membranes in general: freely diffusing membrane proteins without lateral confinement, the presence of a diffusion barrier and interactions with a vesicular coat. We show that protein crowding affects vesicle formation even if the proteins are distributed symmetrically across the membrane and that this effect depends significantly on lateral confinement. The largest crowding effect is predicted for the proteins that are confined to the forming vesicle by a diffusion barrier. We calculate the bending properties of a crowded membrane and find that its spontaneous curvature depends primarily on the degree of transmembrane asymmetry, and its effective bending modulus on the type of lateral confinement. Using the example of COPII vesicle formation from the endoplasmic reticulum, we analyze the energetic cost of vesicle formation. The results provide a novel insight into the effects of lateral and transmembrane organization of membrane proteins, and can guide data interpretation and future experimental approaches.
不对称分布的膜蛋白聚集最近被认为是生物膜重塑的一个重要因素，例如在运输囊泡形成过程中。在本文中，我们从理论上分析了蛋白质聚集对膜弯曲的影响，并研究了其对蛋白质大小、形状、跨膜不对称性和侧向限制的依赖性。我们考虑了三种蛋白质侧向组织的情况，这些情况通常与细胞膜高度相关：无侧向限制的自由扩散膜蛋白、存在扩散屏障以及与囊泡衣被的相互作用。我们表明，即使蛋白质在膜上对称分布，蛋白质聚集也会影响囊泡形成，并且这种影响在很大程度上取决于侧向限制。对于被扩散屏障限制在形成中的囊泡上的蛋白质，预计会有最大的聚集效应。我们计算了拥挤膜的弯曲特性，发现其自发曲率主要取决于跨膜不对称程度，而其有效弯曲模量取决于侧向限制的类型。以内质网形成COPII囊泡为例，我们分析了囊泡形成的能量成本。这些结果为膜蛋白的侧向和跨膜组织的影响提供了新的见解，并可指导数据解释和未来的实验方法。
