PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons

Related Articles
Nuclear Pore Complex: A Flexible Transporter
February 2015
Nuclear Pore Complex: Higher Resolution of Macromolecules
February 2015
Nuclear Pore Complex: Integrative Approach to Probe Nup133
February 2015
Piecing Together the Nuclear Pore Complex
February 2015
Revealing the Nuclear Pore Complex
March 2012
Fit to serve
October 2011
Solutions in the solution
June 2011

Technology Topics Hybrid/Integrative Methods

Nuclear Pore Complex: A Flexible Transporter

SBKB [doi:10.1038/sbkb.2014.243]
Featured Article - February 2015
Short description: Structural flexibility in HEAT motifs enables proteins to pass through the nuclear pore complex.

Structures of importin β from MD simulations in water (a) and 50% [v/v] tetrafluoroethylene/water (b), showing changes in distances between helices. Reproduced from 1, Copyright 2014, with permission from Elsevier.

The nuclear pore complex (NPC) allows proteins to travel between the cytoplasm and nucleus. Small proteins (<40 kDa) can pass through the central channel of the NPC via passive transport, whereas larger proteins require the help of transport receptors. Yoshimura and colleagues recently demonstrated how structural flexibility within transport receptors allows them to chaperone large proteins across the NPC.

One common group of transport receptors, karyopherin β, contains a series of HEAT repeats, each consisting of two amphiphilic α-helices connected by a short linker. The authors used an in vitro transport assay and fluorescence recovery after photobleaching (FRAP) to show that karyopherins, as well as several other HEAT-rich proteins, could pass through the NPC, even though they exceeded the size limit. Karyopherins could also bind to and transport cargo proteins, otherwise excluded from the nucleus, across the NPC. The ability of HEAT-rich proteins to pass through the NPC was attributed to structural dynamics within the motif. Restraining the conformational flexibility of HEAT-rich proteins via a covalently attached crosslinker reduced their ability to traverse the NPC.

To mimic how HEAT motifs act in a hydrophobic environment such as the inside of the NPC channel, the authors studied the effects of hydrophobic solvents on the structure of HEAT-rich proteins. Circular dichroism and fluorescence spectroscopy revealed reversible changes in the tertiary but not secondary structure of HEAT-rich proteins in the presence of hydrophobic solvents. The effect on the tertiary structure was greater as the length of the alkyl group of the solvent increased.

Molecular dynamics (MD) simulations of the HEAT-rich karyopherin importin β provided an explanation for these structural changes: in a hydrophobic solvent, the helices were more spread out, and more hydrophobic residues were exposed to the solvent. Similar results were observed when MD simulations were performed on a complex of importin β with a cargo protein.

This study shows that the structural flexibility afforded by HEAT motifs enables several proteins to pass through the NPC and to carry cargo proteins, despite their large size. This property may be expanded to proteins with other flexible repetitive amphiphilic structural elements.

Jennifer Cable


  1. S.H. Yoshimura, M. Kumeta and S.H. Takeyasu Structural mechanism of nuclear transport mediated by importin β and flexible amphiphilic proteins.
    Structure 22, 1699-1710 (2014). doi:10.1016/j.str.2014.10.009

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health