Global Motions of the Nuclear Pore Complex: Insights from Elastic Network Models

被引:25
作者
Lezon, Timothy R. [1 ]
Sali, Andrej [2 ,3 ]
Bahar, Ivet [1 ]
机构
[1] Univ Pittsburgh, Sch Med, Dept Computat Biol, Pittsburgh, PA 15260 USA
[2] Univ Calif San Francisco, Dept Pharmaceut Chem, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Calif Inst Quantitat Biomed Res, San Francisco, CA 94143 USA
关键词
MESSENGER-RNA EXPORT; ATOMIC-FORCE MICROSCOPY; CRYOELECTRON TOMOGRAPHY; BINDING-DYNAMICS; NUCLEOPORINS; IMPORT; TRANSPORT; GENOME; CONFIGURATIONS; REORGANIZATION;
D O I
10.1371/journal.pcbi.1000496
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The nuclear pore complex (NPC) is the gate to the nucleus. Recent determination of the configuration of proteins in the yeast NPC at similar to 5 nm resolution permits us to study the NPC global dynamics using coarse-grained structural models. We investigate these large-scale motions by using an extended elastic network model (ENM) formalism applied to several coarse-grained representations of the NPC. Two types of collective motions (global modes) are predicted by the ENMs to be intrinsically favored by the NPC architecture: global bending and extension/contraction from circular to elliptical shapes. These motions are shown to be robust against tested variations in the representation of the NPC, and are largely captured by a simple model of a toroid with axially varying mass density. We demonstrate that spoke multiplicity significantly affects the accessible number of symmetric low-energy modes of motion; the NPC-like toroidal structures composed of 8 spokes have access to highly cooperative symmetric motions that are inaccessible to toroids composed of 7 or 9 spokes. The analysis reveals modes of motion that may facilitate macromolecular transport through the NPC, consistent with previous experimental observations.
引用
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页数:10
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