Evidence map›Paper›PMID 32999067›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Functional plasticity and evolutionary adaptation of allosteric regulation.

Megan Leander, Yuchen Yuan, Anthony Meger, Qiang Cui, Srivatsan Raman

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
–field-weighted citation impact
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

57 citing papers in PubMed.

  1. Article
  2. Evolutionary and physics-guided modulation of CaJournal of molecular modeling · 2026
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  20. Genes · 2024
    Article
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

5 authors.

Megan LeanderDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706.
Yuchen YuanDepartment of Chemistry, Boston University, Boston, MA 02215.ORCID 0000-0002-3381-4591
Anthony MegerDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706.
Qiang CuiDepartment of Chemistry, Boston University, Boston, MA 02215.ORCID 0000-0001-6214-5211
Srivatsan RamanDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706; sraman4@wisc.edu.ORCID 0000-0003-2461-1589

Funding

PREDOCTORAL TRAINING IN MOLECULAR BIOPHYSICST32GM008293 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI JACKSON, MEYER B. · 1989 to 2016
$4.6M
Development and application of QM/MM methods for metalloenzymesR01GM106443 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI CUI, QIANG · 2013 to 2020
$2.3M
Understanding molecular rules governing protein allostery by deep mutational scanningDP2GM132682 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI RAMAN, SRIVATSAN · 2018 to 2018
$2.1M
NIGMS NIH HHS DP2 GM132682NIGMS NIH HHS R01 GM106443NIGMS NIH HHS T32 GM008293
6 · The paper itself

Abstract

Allostery is a fundamental regulatory mechanism of protein function. Despite notable advances, understanding the molecular determinants of allostery remains an elusive goal. Our current knowledge of allostery is principally shaped by a structure-centric view, which makes it difficult to understand the decentralized character of allostery. We present a function-centric approach using deep mutational scanning to elucidate the molecular basis and underlying functional landscape of allostery. We show that allosteric signaling exhibits a high degree of functional plasticity and redundancy through myriad mutational pathways. Residues critical for allosteric signaling are surprisingly poorly conserved while those required for structural integrity are highly conserved, suggesting evolutionary pressure to preserve fold over function. Our results suggest multiple solutions to the thermodynamic conditions of cooperativity, in contrast to the common view of a finely tuned allosteric residue network maintained under selection.

Indexed as

Adaptation, PhysiologicalBacterial Physiological PhenomenaBiological EvolutionAllosteric RegulationBacteriaCloning, MolecularEpigenesis, GeneticFlow CytometryGene Expression Regulation, EnzymologicModels, MolecularMolecular Dynamics SimulationMutationProtein Conformationallosterydeep mutational scanningfunctional plasticitymolecular dynamics simulation

Identifiers

PMID32999067
PMCPMC7568325

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.