Evidence map›Paper›PMID 30504143›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2018

Simple yet functional phosphate-loop proteins.

Maria Luisa Romero Romero, Fan Yang, Yu-Ru Lin, Agnes Toth-Petroczy, Igor N Berezovsky, Alexander Goncearenco, Wen Yang, Alon Wellner, Fanindra Kumar-Deshmukh, Michal Sharon and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
4.5field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

59 citing papers in PubMed, 108 citations in OpenAlex.

  1. The history of enzyme evolution embedded in metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. bioRxiv : the preprint server for biology · 2025
    Article
  12. Isoswitching drives the aging process in human brains.bioRxiv : the preprint server for biology · 2025
    Article
  13. On the emergence of metabolism: the evolution of proteins that powered life.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025
    Review
  14. De novo design of ATPase based on a blueprint optimized for harboring the P-loop motif.Protein science : a publication of the Protein Society · 2025
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 6 countries.

Maria Luisa Romero RomeroDepartment of Biomolecular Sciences, Weizmann Institute of Science, 76100 Rehovot, Israel.
Fan YangDepartment of Chemistry, University of Washington, Seattle, WA 98195-1700.
Yu-Ru LinDepartment of Biochemistry, University of Washington, Seattle, WA 98195-1700.
Agnes Toth-PetroczyDepartment of Biomolecular Sciences, Weizmann Institute of Science, 76100 Rehovot, Israel.
Igor N BerezovskyBioinformatics Institute and Agency for Science, Technology and Research, 138671 Singapore.ORCID 0000-0002-3315-8483
Alexander GoncearencoComputational Biology Unit and Department of Informatics, University of Bergen, N-5008 Bergen, Norway.
Wen YangDepartment of Chemistry, University of Washington, Seattle, WA 98195-1700.
Alon WellnerDepartment of Biomolecular Sciences, Weizmann Institute of Science, 76100 Rehovot, Israel.
Fanindra Kumar-DeshmukhDepartment of Biomolecular Sciences, Weizmann Institute of Science, 76100 Rehovot, Israel.
Michal SharonDepartment of Biomolecular Sciences, Weizmann Institute of Science, 76100 Rehovot, Israel.
David BakerDepartment of Biochemistry, University of Washington, Seattle, WA 98195-1700.ORCID 0000-0001-7896-6217
Gabriele VaraniDepartment of Chemistry, University of Washington, Seattle, WA 98195-1700.
Dan S TawfikDepartment of Biomolecular Sciences, Weizmann Institute of Science, 76100 Rehovot, Israel; dan.tawfik@weizmann.ac.il.
University of Washington · USWeizmann Institute of Science · ILAgency for Science, Technology and Research · SGMax Planck Institute of Molecular Cell Biology and Genetics · DENational Institutes of Health · US

Funding

ncRNA: Structure, Interactions and InhibitionR35GM126942 · NIGMS · UNIVERSITY OF WASHINGTON · PI Gabriele Varani · 2018 to 2026
$6.0M
Regulation of microRNA processingR01GM103834 · NIGMS · UNIVERSITY OF WASHINGTON · PI VARANI, GABRIELE · 2014 to 2017
$1.1M
NIGMS NIH HHS R01 GM103834NIGMS NIH HHS R35 GM126942
6 · The paper itself

Abstract

Abundant and essential motifs, such as phosphate-binding loops (P-loops), are presumed to be the seeds of modern enzymes. The Walker-A P-loop is absolutely essential in modern NTPase enzymes, in mediating binding, and transfer of the terminal phosphate groups of NTPs. However, NTPase function depends on many additional active-site residues placed throughout the protein's scaffold. Can motifs such as P-loops confer function in a simpler context? We applied a phylogenetic analysis that yielded a sequence logo of the putative ancestral Walker-A P-loop element: a β-strand connected to an α-helix via the P-loop. Computational design incorporated this element into de novo designed β-α repeat proteins with relatively few sequence modifications. We obtained soluble, stable proteins that unlike modern P-loop NTPases bound ATP in a magnesium-independent manner. Foremost, these simple P-loop proteins avidly bound polynucleotides, RNA, and single-strand DNA, and mutations in the P-loop's key residues abolished binding. Binding appears to be facilitated by the structural plasticity of these proteins, including quaternary structure polymorphism that promotes a combined action of multiple P-loops. Accordingly, oligomerization enabled a 55-aa protein carrying a single P-loop to confer avid polynucleotide binding. Overall, our results show that the P-loop Walker-A motif can be implemented in small and simple β-α repeat proteins, primarily as a polynucleotide binding motif.

Indexed as

Binding SitesProtein Interaction Domains and MotifsAdenosine TriphosphateAmino Acid SequenceCatalytic DomainDNAEvolution, MolecularMagnesiumModels, MolecularMutationNucleoside-TriphosphatasePhosphatesPhylogenyPolynucleotidesProtein BindingProtein ConformationAdenosine TriphosphateDNAMagnesiumNucleoside-TriphosphatasePhosphatesPolynucleotidesProteinsRNARNA-Binding Proteinsconformational diversityde novo protein designprotein evolutionRNA binding proteinWalker-A

Identifiers

PMID30504143
PMCPMC6304952
OpenAlexW2902051551

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.