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Simple rules for passive diffusion through the nuclear pore complex
DOI:10.1083/jcb.201601004.png)
摘要
En 中文
Passive macromolecular diffusion through nuclear pore complexes (NPCs) is thought to decrease dramatically beyond a 30-60-kD size threshold. Using thousands of independent time-resolved fluorescence microscopy measurements in vivo, we show that the NPC lacks such a firm size threshold; instead, it forms a soft barrier to passive diffusion that intensifies gradually with increasing molecular mass in both the wild-type and mutant strains with various subsets of phenylalanine-glycine (FG) domains and different levels of baseline passive permeability. Brownian dynamics simulations replicate these findings and indicate that the soft barrier results from the highly dynamic FG repeat domains and the diffusing macromolecules mutually constraining and competing for available volume in the interior of the NPC, setting up entropic repulsion forces. We found that FG domains with exceptionally high net charge and low hydropathy near the cytoplasmic end of the central channel contribute more strongly to obstruction of passive diffusion than to facilitated transport, revealing a compartmentalized functional arrangement within the NPC.
Keyword:
SMALL-ANGLE SCATTERING
SACCHAROMYCES-CEREVISIAE
NUCLEOCYTOPLASMIC TRANSPORT
FG-NUCLEOPORINS
IN-VIVO
NONSPECIFIC COMPETITION
MOLECULAR ARCHITECTURE
ENVELOPE PERMEABILITY
SPATIAL-ORGANIZATION
DISORDERED PROTEINS
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期刊
IF:
6.4
论文数:
1.2W
被引数:
5.7W
机构
引用论文
Spatiotemporal dynamics of the nuclear pore complex transport barrier resolved by high-speed atomic force microscopy
NATURE NANOTECHNOLOGY
IF34.9
Karyopherin-Centric Control of Nuclear Pores Based on Molecular Occupancy and Kinetic Analysis of Multivalent Binding with FG Nucleoporins
BIOPHYSICAL JOURNAL
IF3.1

