Structural basis of high-affinity nuclear localization signal interactions with importin-alpha

Marfori, Mary, Lonhienne, Thierry G., Forwood, Jade K. and Kobe, Bostjan (2012) Structural basis of high-affinity nuclear localization signal interactions with importin-alpha. Traffic, 13 4: 532-548. doi:10.1111/j.1600-0854.2012.01329.x

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Author Marfori, Mary
Lonhienne, Thierry G.
Forwood, Jade K.
Kobe, Bostjan
Title Structural basis of high-affinity nuclear localization signal interactions with importin-alpha
Formatted title
Structural basis of high-affinity nuclear localization signal interactions with importin-α
Journal name Traffic   Check publisher's open access policy
ISSN 1398-9219
Publication date 2012-04-01
Sub-type Article (original research)
DOI 10.1111/j.1600-0854.2012.01329.x
Open Access Status Not Open Access
Volume 13
Issue 4
Start page 532
End page 548
Total pages 17
Editor Michael S. Marks
Mark C. P. Marsh
Trina A. Schroer
Tom H. Stevens
Place of publication Malden, MA, U.S.A.
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
Classical nuclear localization signals (cNLSs), comprising one (monopartite cNLSs) or two clusters of basic residues connected by a 10-12 residue linker (bipartite cNLSs), are recognised by the nuclear import factor importin-α. The cNLSs bind along a concave groove on importin-α, however, specificity determinants of cNLSs remain poorly understood. We present a structural and interaction analysis study of importin-α binding to both designed and naturally-occurring high-affinity cNLS-like sequences; the peptide inhibitors Bimax1 and Bimax2, and cNLS peptides of cap-binding protein 80. Our data suggest that cNLSs and cNLS-like sequences can achieve high affinity through maximising interactions at the importin-α minor site, and by taking advantage of multiple linker-region interactions. Our study defines an extended set of binding cavities on the importin-α surface, and also expands on recent observations that longer linker sequences are allowed, and that long-range electrostatic complementarity can contribute to cNLS-binding affinity. Altogether, our study explains the molecular and structural basis of the results of a number of recent studies including systematic mutagenesis and peptide library approaches, and provides an improved level of understanding on the specificity determinants of a cNLS. Our results have implications for identifying cNLSs in novel proteins.
Keyword Importin-α
Nuclear localization sequence (NLS)
Nucleo-cytoplasmic transport
Cap-binding protein 80 (CBP80)
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Centre for Integrative Legume Research Publications
Official 2013 Collection
School of Chemistry and Molecular Biosciences
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Citation counts: TR Web of Science Citation Count  Cited 46 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 49 times in Scopus Article | Citations
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Created: Thu, 19 Jan 2012, 18:25:46 EST by Lucy O'Brien on behalf of School of Chemistry & Molecular Biosciences