European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, Netherlands.
European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, Netherlands; Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, Groningen 9747 AG, The Netherlands; Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, Groningen 9747 AG, The Netherlands.
Structure. 2020 Feb 4;28(2):185-195.e5. doi: 10.1016/j.str.2019.11.003. Epub 2019 Dec 2.
The nuclear pore complex (NPC) is embedded in the nuclear envelope and forms the main gateway to the nuclear interior including the inner nuclear membrane (INM). Two INM proteins in yeast are selectively imported. Their sorting signals consist of a nuclear localization signal, separated from the transmembrane domain by a long intrinsically disordered (ID) linker. We used computational models to predict the dynamic conformations of ID linkers and analyzed the INM targeting efficiency of proteins with linker regions with altered Stokes radii and decreased flexibilities. We find that flexibility, Stokes radius, and the frequency at which the linkers are at an extended end-to-end distance larger than 25 nm are good predictors for the targeting of the proteins. The data are consistent with a transport mechanism in which INM targeting of Heh2 is dependent on an ID linker that facilitates the crossing of the approximately 25-nm thick NPC scaffold.
核孔复合体（NPC）嵌入核膜中，形成进入核内部的主要通道，包括内核膜（INM）。酵母中有两种 INM 蛋白被选择性地输入。它们的分选信号由一个核定位信号组成，该信号通过一个长的固有无序（ID）连接子与跨膜结构域分离。我们使用计算模型来预测 ID 连接子的动态构象，并分析具有改变的斯托克斯半径和降低的柔韧性的连接子区域的蛋白质的 INM 靶向效率。我们发现，柔韧性、斯托克斯半径以及连接子处于伸展的末端到末端距离大于 25nm 的频率是蛋白质靶向的良好预测因子。这些数据与一种运输机制一致，其中 Heh2 的 INM 靶向依赖于一个 ID 连接子，该连接子有助于穿过大约 25nm 厚的 NPC 支架。
