Evidence map›Paper›PMID 32079772›Full record

ArticleScience (New York, N.Y.)2020

Ancient origins of allosteric activation in a Ser-Thr kinase.

Adelajda Hadzipasic, Christopher Wilson, Vy Nguyen, Nadja Kern, Chansik Kim, Warintra Pitsawong, Janice Villali, Yuejiao Zheng, Dorothee Kern

Open access · greenAbstract read
In one paragraph

Article in Science (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing 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

27 citing papers in PubMed, 64 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. A billion years of evolution manifest in nanosecond protein dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  10. Article
  11. Emerging maps of allosteric regulation in cellular networks.Current opinion in structural biology · 2023
    Review
  12. Article
  13. Article
  14. Article
  15. Calculation of centralities in protein kinase A.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Dynamic equilibria in protein kinases.Current opinion in structural biology · 2021
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Adelajda HadzipasicDepartment of Biochemistry, Brandeis University, Waltham, MA 02454, USA.ORCID 0000-0002-4452-8419
Christopher WilsonDepartment of Biochemistry, Brandeis University, Waltham, MA 02454, USA.ORCID 0000-0002-8012-2440
Vy NguyenDepartment of Biochemistry, Brandeis University, Waltham, MA 02454, USA.ORCID 0000-0002-9484-7557
Nadja KernDepartment of Biochemistry, Brandeis University, Waltham, MA 02454, USA.ORCID 0000-0002-1313-5890
Chansik KimDepartment of Biochemistry, Brandeis University, Waltham, MA 02454, USA.ORCID 0000-0002-0043-0276
Warintra PitsawongDepartment of Biochemistry, Brandeis University, Waltham, MA 02454, USA.
Janice VillaliDepartment of Biochemistry, Brandeis University, Waltham, MA 02454, USA.
Yuejiao ZhengDepartment of Biochemistry, Brandeis University, Waltham, MA 02454, USA.
Dorothee KernDepartment of Biochemistry, Brandeis University, Waltham, MA 02454, USA. dkern@brandeis.edu.ORCID 0000-0002-7631-8328
Howard Hughes Medical Institute · US

Funding

Collaborative experimental & computational studies of conformational transitionsR01GM100966 · NIGMS · BRANDEIS UNIVERSITY · PI HAGAN, MICHAEL F, KERN, DOROTHEE · 2013 to 2016
$1.2M
European Research CouncilHoward Hughes Medical InstituteNIGMS NIH HHS R01 GM100966
6 · The paper itself

Abstract

A myriad of cellular events are regulated by allostery; therefore, evolution of this process is of fundamental interest. Here, we use ancestral sequence reconstruction to resurrect ancestors of two colocalizing proteins, Aurora A kinase and its allosteric activator TPX2 (targeting protein for Xklp2), to experimentally characterize the evolutionary path of allosteric activation. Autophosphorylation of the activation loop is the most ancient activation mechanism; it is fully developed in the oldest kinase ancestor and has remained stable over 1 billion years of evolution. As the microtubule-associated protein TPX2 appeared, efficient kinase binding to TPX2 evolved, likely owing to increased fitness by virtue of colocalization. Subsequently, TPX2-mediated allosteric kinase regulation gradually evolved. Surprisingly, evolution of this regulation is encoded in the kinase and did not arise by a dominating mechanism of coevolution.

Indexed as

Evolution, MolecularAllosteric RegulationAnimalsAurora Kinase ACell Cycle ProteinsEnzyme ActivationHumansMicrotubule-Associated ProteinsPhylogenyAurora Kinase ACell Cycle ProteinsMicrotubule-Associated ProteinsTPX2 protein, human

Identifiers

PMID32079772
PMCPMC9617290
OpenAlexW3007100485

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.