Minasbekyan Liya A, Badalyan Hamlet G
Scientific Research Institute of Biology, Yerevan State University, A. Manoogian St., 1, 0025 Yerevan, Armenia.
Chair of General Physics, Yerevan State University, A. Manoogian St., 1, 0025 Yerevan, Armenia.
Biophys Rev. 2023 Oct 4;15(5):1195-1207. doi: 10.1007/s12551-023-01136-8. eCollection 2023 Oct.
Nuclear cytoplasmic transport is mediated by many receptors that recognize specific nuclear localization signals on proteins and RNA and transport these substrates through nuclear pore complexes. Facilitated diffusion through nuclear pore complexes requires the attachment of transport receptors. Despite the relatively large tunnel diameter, some even small proteins (less than 20-30 kDa), such as histones, pass through the nuclear pore complex only with transport receptors. Over several decades, considerable material has been accumulated on the structure, architecture, and amino acid composition of the proteins included in this complex and the sequence of many receptors. We consider the data available in the literature on the structure of the nuclear pore complex and possible mechanisms of nuclear-cytoplasmic transport, applying the theory of electrostatic interactions in the context of our data on changes in the electrokinetic potential of nuclei and our previously proposed physical model of the mechanism of facilitated diffusion through the nuclear pore complex (NPC). According to our data, the main contribution to the charge of the nuclear membrane is made by anionic phospholipids, which are part of both the nuclear membrane and the nuclear matrix, which creates a potential difference between them. The nuclear membrane is a four-layer phospholipid dielectric, so the potential vector can only pass through the NPC, creating an electrostatic funnel that "pulls in" the positively charged load-NLS-NTR trigger complexes. Considering the newly obtained data, an improved model of the previously proposed physical model of the mechanism of nuclear-cytoplasmic transport is proposed. This model considers the contribution of electrostatic fields to the transportation speed when changing the membrane's thickness in the NPC basket at a higher load.
核质运输由许多受体介导，这些受体识别蛋白质和RNA上的特定核定位信号，并通过核孔复合体运输这些底物。通过核孔复合体的易化扩散需要运输受体的附着。尽管核孔复合体的通道直径相对较大，但一些甚至小的蛋白质（小于20 - 30 kDa），如组蛋白，只有与运输受体一起才能通过核孔复合体。几十年来，关于该复合体中所含蛋白质的结构、结构组成和氨基酸组成以及许多受体的序列，已经积累了大量资料。我们结合关于细胞核电动电位变化的数据以及我们先前提出的通过核孔复合体易化扩散机制的物理模型，应用静电相互作用理论，考虑文献中关于核孔复合体结构和核质运输可能机制的数据。根据我们的数据，核膜电荷的主要贡献来自阴离子磷脂，它们是核膜和核基质的一部分，这在它们之间产生了电位差。核膜是四层磷脂介质，所以电位向量只能通过核孔复合体，形成一个静电漏斗，“拉入”带正电荷的负载 - NLS - NTR触发复合体。考虑到新获得的数据，提出了先前提出的核质运输机制物理模型的改进模型。该模型考虑了在较高负载下改变核孔复合体篮状结构中膜厚度时静电场对运输速度的贡献。
