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Six Classes of Nuclear Localization Signals Specific to Different Binding Grooves of Importin α

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Kosugi, Shunichi, Hasebe, Masako, Matsumura, Nobutaka, Takashima, Hideaki, Miyamoto-Sato, Etsuko, Tomita, Masaru, Yanagawa, Hiroshi·2009·Journal of Biological Chemistry

Abstract

The importin alpha/beta pathway mediates nuclear import of proteins containing the classical nuclear localization signals (NLSs). Although the consensus sequences of the classical NLSs have been defined, there are still many NLSs that do not match the consensus rule and many nonfunctional sequences that match the consensus. We report here six different NLS classes that specifically bind to distinct binding pockets of importin alpha. By screening of random peptide libraries using an mRNA display, we selected peptides bound by importin alpha and identified six classes of NLSs, including three novel classes. Two noncanonical classes (class 3 and class 4) specifically bound the minor binding pocket of importin alpha, whereas the classical monopartite NLSs (class 1 and class 2) bound to the major binding pocket. Using a newly developed universal green fluorescent protein expression system, we found that these NLS classes, including plant-specific class 5 NLSs and bipartite NLSs, fundamentally require the regions outside the core basic residues for their activity and have specific residues or patterns that confer the activities differently between yeast, plants, and mammals. Furthermore, amino acid replacement analyses revealed that the consensus basic patterns of the classical NLSs are not essential for activity, thereby generating more unconventional patterns, including redox-sensitive NLSs. These results explain the causes of the NLS diversity. The defined consensus patterns and properties of importin alpha-dependent NLSs provide useful information for identifying NLSs.

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Metadata

Authors
Kosugi, S., Hasebe, M., Matsumura, N., Takashima, H., Miyamoto-Sato, E., Tomita, M., & Yanagawa, H.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2009-01
Volume
284
Issue
1
Pages
478-485
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1976572901
Cited by
615
References
37
FWCI
5.21
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Six Classes of Nuclear Localization Signals Specific to Different Binding Grooves of Importin α. https://app.cochat.ai/papers/10.1074/jbc.m807017200
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Kosugi, S., Hasebe, M., Matsumura, N., Takashima, H., Miyamoto-Sato, E., Tomita, M., & Yanagawa, H. (2009). Six Classes of Nuclear Localization Signals Specific to Different Binding Grooves of Importin α. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m807017200

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