Fusion crystallization reveals the behavior of both the 1TEL crystallization chaperone and the TNK1 UBA domain
Open accessPublished version of a preprint
Abstract
Human thirty-eight-negative kinase-1 (TNK1) is implicated in cancer progression. The TNK1 ubiquitin-associated (UBA) domain binds polyubiquitin and plays a regulatory role in TNK1 activity and stability. No experimentally determined molecular structure of this unusual UBA domain is available. We fused the UBA domain to the 1TEL variant of the translocation ETS leukemia protein sterile alpha motif (TELSAM) crystallization chaperone and obtained crystals diffracting as far as 1.53 Å. GG and GSGG linkers allowed the UBA to reproducibly find a productive binding mode against its host 1TEL polymer and crystallize at protein concentrations as low as 0.2 mg/mL. Our studies support a mechanism of 1TEL fusion crystallization and show that 1TEL fusion crystals require fewer crystal contacts than traditional protein crystals. Modeling and experimental validation suggest the UBA domain may be selective for both the length and linkages of polyubiquitin chains.
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
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.
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 · see citing works
A Designed Conformational Shift To Control Protein Binding Specificity
Michielssens, S., Peters, J. H., Ban, D., Pratihar, S., Seeliger, D., Sharma, M., Giller, K., Sabo, T. M., Becker, S., Lee, D., et al. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201403102 · Cited by 54 · see citing works
Flagged first, then by citations
- Authors
- Nawarathnage, S., Tseng, Y. J., Soleimani, S., Smith, T., Pedroza Romo, M. J., Abiodun, W. O., Egbert, C. M., Madhusanka, D., Bunn, D., Woods, B., Tsubaki, E., Stewart, C., Brown, S., Doukov, T., Andersen, J. L., & Moody, J. D.
- Affiliations
- Brigham Young University (US)
- Stanford Synchrotron Radiation Lightsource (US)
- Corresponding author
- Andersen, Joshua L.
- Moody, James D.
- ORCID
- Venue
- Structure
- Publisher
- Elsevier BV
- Published
- 2023-12
- Volume
- 31
- Issue
- 12
- Pages
- 1589-1603.e6
- ISSN
- 0969-2126 (ISSN-L)
- PMC
- PMC10843481
- OpenAlex
- W4387208815
- Cited by
- 6
- References
- 2
- Citations by year
- 2026: 2 · 2025: 4
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Structure (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- Funders
- U.S. Department of Energy (76SF00515, DE–AC02–76SF00515, AC02‐76SF00515, P30-GM133894, DE-AC02-)
- National Institutes of Health (1r01gm147310-01, NIH-R01, DE-AC02-76SF00515, R01 GM147310-01)
- Office of Science (AC02-76SF00515, DE-AC02-76SF0051 5, DE-AC02, 76SF00515)
- National Institute of General Medical Sciences (GM146209, R01GM147310, DE-AC02-76SF00515, R15GM146209, GM147310-01, P30GM133894)
- Basic Energy Sciences (DE-AC02, 76SF00515, AC02-76SF00515, DE-AC-02-76SF00515)
- Biological and Environmental Research (DE- AC0276SF00515, P30GM133894)
- SLAC National Accelerator Laboratory (DEAC02−76SF00515, AC02‐76SF00515)
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- TNK1, UBA domain, crystallization chaperones, protein-protein complex structure, crystal contacts, tumor progression
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
