ArticlePLoS biology2008
Modular organization and combinatorial energetics of proline-tyrosine nuclear localization signals.
Article in PLoS biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 84 citations in OpenAlex.
- A systematic interactome ofeLife · 2026Article
- Multiple roads between the nucleus and the cytoplasm: classes of linear NLSs and NESs and their receptors.Current opinion in structural biology · 2026Review
- Exploration of the proxiOME of large subunit ribosomal proteins reveals Acl1 and Bcl1 as cooperating dedicated chaperones of Rpl1.Nucleic acids research · 2026Article
- A new Karyopherin-β2 binding PY-NLS epitope of HNRNPH2 linked to neurodevelopmental disorders.Structure (London, England : 1993) · 2023Article
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- Proteomic elucidation of the targets and primary functions of the picornavirus 2A protease.The Journal of biological chemistry · 2022Article
- Karyopherin-mediated nucleocytoplasmic transport.Nature reviews. Molecular cell biology · 2022Review
- Distinct mutations in importin-β family nucleocytoplasmic transport receptors transportin-SR and importin-13 affect specific cargo binding.Scientific reports · 2021Article
- Characterization of HNRNPA1 mutations defines diversity in pathogenic mechanisms and clinical presentation.JCI insight · 2021Article
- Nucleocytoplasmic Transport: Regulatory Mechanisms and the Implications in Neurodegeneration.International journal of molecular sciences · 2021Review
- Transportin-1: A Nuclear Import Receptor with Moonlighting Functions.Frontiers in molecular biosciences · 2021Review
- Nucleolar localization of the yeast RNA exosome subunit Rrp44 hints at early pre-rRNA processing as its main function.The Journal of biological chemistry · 2020Article
- Karyopherins and condensates.Current opinion in cell biology · 2020Review
- Review
- The coming-of-age of nucleocytoplasmic transport in motor neuron disease and neurodegeneration.Cellular and molecular life sciences : CMLS · 2019Review
- High-mobility group box 1 links sensing of reactive oxygen species by huntingtin to its nuclear entry.The Journal of biological chemistry · 2019Article
- Alternative splicing regulates distinct subcellular localization of Epithelial splicing regulatory protein 1 (Esrp1) isoforms.Scientific reports · 2017Article
- Extensive cargo identification reveals distinct biological roles of the 12 importin pathways.eLife · 2017Article
- Distinctive Nuclear Localization Signals in the OomyceteFrontiers in microbiology · 2017Article
- Karyopherin-β2 Recognition of a PY-NLS Variant that Lacks the Proline-Tyrosine Motif.Structure (London, England : 1993) · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Proline-tyrosine nuclear localization signals (PY-NLSs) are recognized and transported into the nucleus by human Karyopherin (Kap) beta2/Transportin and yeast Kap104p. Multipartite PY-NLSs are highly diverse in sequence and structure, share a common C-terminal R/H/KX2-5PY motif, and can be subdivided into hydrophobic and basic subclasses based on loose N-terminal sequence motifs. PY-NLS variability is consistent with weak consensus motifs, but such diversity potentially renders comprehensive genome-scale searches intractable. Here, we use yeast Kap104p as a model system to understand the energetic organization of this NLS. First, we show that Kap104p substrates contain PY-NLSs, demonstrating their generality across eukaryotes. Previously reported Kapbeta2-NLS structures explain Kap104p specificity for the basic PY-NLS. More importantly, thermodynamic analyses revealed physical properties that govern PY-NLS binding affinity: (1) PY-NLSs contain three energetically significant linear epitopes, (2) each epitope accommodates substantial sequence diversity, within defined limits, (3) the epitopes are energetically quasi-independent, and (4) a given linear epitope can contribute differently to total binding energy in different PY-NLSs, amplifying signal diversity through combinatorial mixing of energetically weak and strong motifs. The modular organization of the PY-NLS coupled with its combinatorial energetics lays a path to decode this diverse and evolvable signal for future comprehensive genome-scale identification of nuclear import substrates.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.