Structural basis of recognition of monopartite and bipartite nuclear localization sequences by mammalian importin-α11Edited by K. Nagai
Abstract
Importin-alpha is the nuclear import receptor that recognizes cargo proteins which contain classical monopartite and bipartite nuclear localization sequences (NLSs), and facilitates their transport into the nucleus. To determine the structural basis of the recognition of the two classes of NLSs by mammalian importin-alpha, we co-crystallized an N-terminally truncated mouse receptor protein with peptides corresponding to the monopartite NLS from the simian virus 40 (SV40) large T-antigen, and the bipartite NLS from nucleoplasmin. We show that the monopartite SV40 large T-antigen NLS binds to two binding sites on the receptor, similar to what was observed in yeast importin-alpha. The nucleoplasmin NLS-importin-alpha complex shows, for the first time, the mode of binding of bipartite NLSs to the receptor. The two basic clusters in the NLS occupy the two binding sites used by the monopartite NLS, while the sequence linking the two basic clusters is poorly ordered, consistent with its tolerance to mutations. The structures explain the structural basis for binding of diverse NLSs to the sole receptor protein.
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NLSs can be recognized by importin α, nuclear import receptor, and trigger subsequent transportation from cytosol to nucleus.
“NLSs can be recognized by importin α, the nuclear import receptor, and trigger the subsequent transportation from the cytosol to the nucleus [198].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [198]
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- Authors
- Fontes, M. R. M., Teh, T., & Kobe, B.
- Affiliations
- St Vincents Institute of Medical Research (AU)
- ORCID
- Fontes, Marcos R.M.
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2000-04
- Volume
- 297
- Issue
- 5
- Pages
- 1183-1194
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W2049132410
- Cited by
- 398
- References
- 45
- Citations by year
- 2026: 15 · 2025: 12 · 2024: 7 · 2023: 14 · 2022: 15 · 2021: 16 · 2020: 11 · 2019: 8 · 2018: 12 · 2017: 19 · 2016: 19 · 2015: 25 · 2014: 10 · 2013: 20 · 2012: 13
- Type
- book review
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- nuclear localization signal, bipartite NLS, nuclear import, SV40 large T antigen, nucleoplasmin, protein-peptide complex structure, receptor binding sites, nuclear transport receptors
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, Models, Molecular, Molecular Sequence Data, Mutation, Nuclear Proteins, Oligopeptides, Peptide Fragments, Phosphoproteins, Protein Binding, Structure-Activity Relationship, Substrate Specificity, Yeasts, Conserved Sequence, Protein Structure, Secondary, Protein Structure, Tertiary, Crystallography, X-Ray, Nuclear Localization Signals, Karyopherins, Mice, Nucleoplasmins
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