ArticleNature communications2017
Correlation of fitness landscapes from three orthologous TIM barrels originates from sequence and structure constraints.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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.
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.
Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Fitness translocation: improving variant effect prediction with biologically-grounded data augmentation.Bioinformatics (Oxford, England) · 2026Article
- Seven complete comparative maps of allosteric mutations in a protein family.Nature communications · 2026Article
- Enhancing kCommunications biology · 2026Article
- Robust enzyme discovery and engineering with deep learning using CataPro.Nature communications · 2025Article
- Understanding epistatic networks in the B1 β-lactamases through coevolutionary statistical modeling and deep mutational scanning.Nature communications · 2024Article
- A systematic analysis of regression models for protein engineering.PLoS computational biology · 2024Article
- Rheostats, toggles, and neutrals, Oh my! A new framework for understanding how amino acid changes modulate protein function.The Journal of biological chemistry · 2024Review
- Stepwise introduction of stabilizing mutations reveals nonlinear additive effects in de novo TIM barrels.Protein science : a publication of the Protein Society · 2024Article
- ProteinGym: Large-Scale Benchmarks for Protein Design and Fitness Prediction.bioRxiv : the preprint server for biology · 2023Article
- Jointly modeling deep mutational scans identifies shifted mutational effects among SARS-CoV-2 spike homologs.bioRxiv : the preprint server for biology · 2023Article
- PYK-SubstitutionOME: an integrated database containing allosteric coupling, ligand affinity and mutational, structural, pathological, bioinformatic and computational information about pyruvate kinase isozymes.Database : the journal of biological databases and curation · 2023Article
- Odd one out? Functional tuning of Zymomonas mobilis pyruvate kinase is narrower than its allosteric, human counterpart.Protein science : a publication of the Protein Society · 2022Article
- Article
- Shifts in amino acid preferences as proteins evolve: A synthesis of experimental and theoretical work.Protein science : a publication of the Protein Society · 2021Review
- Evolution, folding, and design of TIM barrels and related proteins.Current opinion in structural biology · 2021Review
- A conserved folding nucleus sculpts the free energy landscape of bacterial and archaeal orthologs from a divergent TIM barrel family.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Rewards of divergence in sequences, 3-D structures and dynamics of yeast and human spliceosome SF3b complexes.Current research in structural biology · 2021Article
- Article
- An allosteric pathway explains beneficial fitness in yeast for long-range mutations in an essential TIM barrel enzyme.Protein science : a publication of the Protein Society · 2020Article
- Rheostat positions: A new classification of protein positions relevant to pharmacogenomics.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Sequence divergence of orthologous proteins enables adaptation to environmental stresses and promotes evolution of novel functions. Limits on evolution imposed by constraints on sequence and structure were explored using a model TIM barrel protein, indole-3-glycerol phosphate synthase (IGPS). Fitness effects of point mutations in three phylogenetically divergent IGPS proteins during adaptation to temperature stress were probed by auxotrophic complementation of yeast with prokaryotic, thermophilic IGPS. Analysis of beneficial mutations pointed to an unexpected, long-range allosteric pathway towards the active site of the protein. Significant correlations between the fitness landscapes of distant orthologues implicate both sequence and structure as primary forces in defining the TIM barrel fitness landscape and suggest that fitness landscapes can be translocated in sequence space. Exploration of fitness landscapes in the context of a protein fold provides a strategy for elucidating the sequence-structure-fitness relationships in other common motifs.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.