Evidence map›Paper›PMID 19749752›Full record

ArticleNature structural & molecular biology2009

Following evolutionary paths to protein-protein interactions with high affinity and selectivity.

Kalia Bernath Levin, Orly Dym, Shira Albeck, Shlomo Magdassi, Anthony H Keeble, Colin Kleanthous, Dan S Tawfik

Abstract read
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In one paragraph

Article in Nature structural & molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing 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

48 citing papers in PubMed.

  1. Article
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  5. Addressing epistasis in the design of protein function.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  6. Article
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  9. Affinity of disordered protein complexes is modulated by entropy-energy reinforcement.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  10. Review
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  19. Low-stringency selection of TEM1 for BLIP shows interface plasticity and selection for faster binders.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  20. 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

7 authors.

Kalia Bernath LevinDepartment of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
Orly Dym
Shira Albeck
Shlomo Magdassi
Anthony H Keeble
Colin Kleanthous
Dan S Tawfik

Funding

Biotechnology and Biological Sciences Research Council BB/E011306/1
6 · The paper itself

Abstract

How do intricate multi-residue features such as protein-protein interfaces evolve? To address this question, we evolved a new colicin-immunity binding interaction. We started with Im9, which inhibits its cognate DNase ColE9 at 10(-14) M affinity, and evolved it toward ColE7, which it inhibits promiscuously (Kd > 10(-8) M). Iterative rounds of random mutagenesis and selection toward higher affinity for ColE7, and selectivity (against ColE9 inhibition), led to an approximately 10(5)-fold increase in affinity and a 10(8)-fold increase in selectivity. Analysis of intermediates along the evolved variants revealed that changes in the binding configuration of the Im protein uncovered a latent set of interactions, thus providing the key to the rapid divergence of new Im7 variants. Overall, protein-protein interfaces seem to share the evolvability features of enzymes, that is, the exploitation of promiscuous interactions and alternative binding configurations via 'generalist' intermediates, and the key role of compensatory stabilizing mutations in facilitating the divergence of new functions.

Indexed as

Protein Interaction MappingColicinsDeoxyribonucleasesEpistasis, GeneticEvolution, MolecularKineticsModels, MolecularMolecular ConformationMutagenesisMutationPhenotypeProtein BindingRecombination, GeneticColE7 protein, E coliColicinsDeoxyribonucleases

Identifiers

PMID19749752

What OpenQuestion holds

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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.