The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Sequence specificity of an essential nuclear localization sequence in Mcm3
Open accessPreprint — published as 10.1371/journal.pgen.1011499
Abstract
Proteins with nuclear localization sequences (NLSs) are directed into the cell nucleus through interactions between the NLS and importin proteins. NLSs are generally short motifs rich in basic amino acids; however, identifying NLSs can be challenging due to the lack of a universally conserved sequence. In this study, we characterized the sequence specificity of an essential and conserved NLS in Mcm3, a subunit of the replicative DNA helicase. Through mutagenesis and AlphaFold 3 (AF3) modeling, we demonstrate that the precise positioning of basic residues within the NLS is critical for nuclear transport of Mcm3 through optimal interactions with importin. Disrupting these interactions impairs the nuclear import of Mcm3, resulting in defective chromatin loading of MCM and poor cell growth. Our results provide a structure-guided framework for predicting and analyzing monopartite NLSs, which, despite lacking a single consensus sequence, retain key characteristics shared between the NLSs of Mcm3 and the SV40 large T antigen. Author Summary: Transporting proteins into and out of the cell nucleus is essential for chromosome-associated activities. Nuclear localization sequences (NLSs), short motifs rich in basic amino acids, are commonly found in nuclear proteins. NLSs work by interacting with importin, a key transport receptor responsible for recognizing and guiding NLS-containing proteins through the nuclear pore complex into the nucleus. Other than being rich in basic amino acids, NLSs generally lack a discernible consensus sequence, raising questions about how they specifically control nuclear transport through their interactions with importins. Through a detailed mutagenesis study of a conserved and essential NLS in Mcm3, a subunit of the replicative DNA helicase, we demonstrate that the use of AlphaFold 3 (AF3), alongside genetic, biochemical, and cell biological analyses, define key contacts between Mcm3’s NLS and importin that are required for nuclear import of Mcm3.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Flagged first, then by citations
Research works printed but not linked: 47
- 10.1186/s12964-021-00741-y · DOI
- 10.1016/0968-0004(91)90184-W · DOI
- 10.1074/jbc.R600026200 · DOI
- 10.1016/S0092-8674(00)81419-1 · DOI
- 10.1128/MCB.7.11.4048 · DOI
- 10.1073/pnas.89.10.4290 · DOI
- 10.1128/MCB.8.10.4048 · DOI
- 10.1091/mbc.E05-05-0412 · DOI
- 10.1046/j.1365-2443.1997.1510349.x · DOI
- 10.1074/jbc.273.35.22177 · DOI
- 10.1016/0092-8674(84)90457-4 · DOI
- 10.1016/0092-8674(91)90245-T · DOI
- 1993, Nuclear localization signals (NLS), Crit Rev Eukaryot Gene Expr, 3, 193
- 10.1146/annurev.cellbio.15.1.607 · DOI
- 10.1016/S0969-2126(00)00107-6 · DOI
- 10.1038/s41467-018-05928-5 · DOI
- 10.1016/j.bbrc.2019.01.075 · DOI
- 10.1006/jmbi.2000.3642 · DOI · Paper page
- 10.1016/0092-8674(84)90415-X · DOI
- 10.1128/MCB.6.11.4136 · DOI
- 10.1101/gad.5.6.944 · DOI
- 10.1016/0378-1119(94)00925-I · DOI
- 10.1091/mbc.12.11.3658 · DOI
- 10.1093/genetics/106.3.365 · DOI
- 10.1038/s41467-017-02389-0 · DOI
- 10.1038/nature11920 · DOI
- 10.1016/S0167-4781(98)00033-5 · DOI
- 10.1038/nature14685 · DOI
- 10.1073/pnas.1712537114 · DOI
- 10.1091/mbc.8.8.1587 · DOI
- 10.1101/gad.7.11.2149 · DOI
- 10.1016/S0167-4781(98)00033-5 · DOI
- 10.1046/j.1365-2443.1996.840284.x · DOI
- 10.1083/jcb.129.6.1433 · DOI
- 10.1159/000094103 · DOI
- 10.1073/pnas.94.11.5611 · DOI
- 10.1101/gad.11.24.3375 · DOI
- 10.1016/j.molcel.2004.11.038 · DOI
- 10.1074/jbc.270.28.16499 · DOI
- 10.1371/journal.pgen.1010275 · DOI
- 10.1007/s00018-003-3070-3 · DOI
- 10.1038/s41586-024-07487-w · DOI · Paper page
- 10.1186/1471-2105-10-202 · DOI
- 10.1186/s12985-019-1153-5 · DOI
- 10.1016/S0021-9258(17)35282-1 · DOI
- 10.1016/j.cell.2009.10.015 · DOI
- 10.1016/j.ymeth.2012.06.008 · DOI
Metadata
- Authors
- Wang, Z., Zhang, Y. J., Zhang, Q.-Y., Bilsborrow, K., Leslie, M., Suhandynata, R. T., & Zhou, H.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Zhou, Huilin
- Venue
- PLoS Genetics
- Publisher
- openRxiv
- Published
- 2024-11-14
- Volume
- 21
- Issue
- 1
- Pages
- e1011499-e1011499
- ISSN
- 1553-7390 (ISSN-L)
- PMC
- PMC11761085
- OpenAlex
- W4406657397
- Cited by
- 2
- References
- 1
- Citations by year
- 2026: 2
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Francis Crick Institute
- Academy of Finland
- National Institutes of Health
- Centers for Disease Control and Prevention
- University of California, San Diego
- National Institute of General Medical Sciences (GM151191, R01GM116897, R01GM151191, GM116897)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- nuclear localization signal, MCM3, nuclear import, importins, DNA helicase, MCM complex, chromatin loading, basic residues, SV40 large T antigen, sequence specificity, AlphaFold3
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
