Ankur Mishra, Erik Van der Giessen, Patrick R Onck
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引用次数: 0
Abstract
The nuclear pore complex (NPC) is responsible for the selective transport of biomolecules in and out of the nucleus. This selective feature is achieved through intrinsically disordered proteins, FG-nups, that are anchored to the inner wall of the NPC. Cargo smaller than approximately 5 nm can rapidly diffuse through the NPC whereas larger cargo is increasingly slowed down. Larger cargos bound to chaperone proteins (from the karyopherin or Kap family) can still be transported due to non-specific interactions with the FG-Nups. Although various mechanisms for the transport of Kaps have been proposed, a consensus has still to be reached. Here we conducted a coarse-grained molecular dynamics study to shed light on Kap translocation through NPCs. We investigated the effect of Kap surface charge and hydrophobicity on the transport rate. We found that the negative charge of the Kaps is essential for transport whereas Kap hydrophobicity of the transport particle aids in the translocation. Interestingly, our results indicate that the positive net charge of the nuclear Nups (especially Nup1) is instrumental for the transport of Kaps, revealing a (previously proposed) gradient of increasing binding affinity of the Kaps with FG-Nups from the cytoplasm to the nucleus.
期刊介绍:
BJ publishes original articles, letters, and perspectives on important problems in modern biophysics. The papers should be written so as to be of interest to a broad community of biophysicists. BJ welcomes experimental studies that employ quantitative physical approaches for the study of biological systems, including or spanning scales from molecule to whole organism. Experimental studies of a purely descriptive or phenomenological nature, with no theoretical or mechanistic underpinning, are not appropriate for publication in BJ. Theoretical studies should offer new insights into the understanding ofexperimental results or suggest new experimentally testable hypotheses. Articles reporting significant methodological or technological advances, which have potential to open new areas of biophysical investigation, are also suitable for publication in BJ. Papers describing improvements in accuracy or speed of existing methods or extra detail within methods described previously are not suitable for BJ.