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Cited by 81Protein Structure and DynamicsOrigins and Evolution of LifeRNA and protein synthesis mechanisms

The TIM Barrel Architecture Facilitated the Early Evolution of Protein-Mediated Metabolism

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Goldman, Aaron David, Beatty, Joshua T., Landweber, Laura F.·2016·Journal of Molecular Evolution
DOI 10.1007/s00239-015-9722-8PMC PMC4709378
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Abstract

The triosephosphate isomerase (TIM) barrel protein fold is a structurally repetitive architecture that is present in approximately 10% of all enzymes. It is generally assumed that this ubiquity in modern proteomes reflects an essential historical role in early protein-mediated metabolism. Here, we provide quantitative and comparative analyses to support several hypotheses about the early importance of the TIM barrel architecture. An information theoretical analysis of protein structures supports the hypothesis that the TIM barrel architecture could arise more easily by duplication and recombination compared to other mixed α/β structures. We show that TIM barrel enzymes corresponding to the most taxonomically broad superfamilies also have the broadest range of functions, often aided by metal and nucleotide-derived cofactors that are thought to reflect an earlier stage of metabolic evolution. By comparison to other putatively ancient protein architectures, we find that the functional diversity of TIM barrel proteins cannot be explained simply by their antiquity. Instead, the breadth of TIM barrel functions can be explained, in part, by the incorporation of a broad range of cofactors, a trend that does not appear to be shared by proteins in general. These results support the hypothesis that the simple and functionally general TIM barrel architecture may have arisen early in the evolution of protein biosynthesis and provided an ideal scaffold to facilitate the metabolic transition from ribozymes, peptides, and geochemical catalysts to modern protein enzymes.

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  • Present-day low molecular weight cofactors may have been early non-protein catalysts.

    “This notion obtains further support from the experiment-based proposals that present-day low molecular weight cofactors may have been early non-protein catalysts [32,204,205,213,214].”

    From Systems protobiology: origin of life in lipid catalytic networks (2018) · cites this paper as [214]

    The Introduction (page unavailable) says that modern enzyme cofactors reflect an earlier period when ribozymes, peptides, metals, and minerals catalyzed reactions. The Results and Discussion specifically links inorganic cofactors to ancient mineral and ion catalysts, but does not say that present-day cofactors generally acted as independent non-protein catalysts. The paper describes its own work as analyses, not experiments, so it does not substantiate the sentence’s “experiment-based” characterization of this source. (LLM, conf=0.83)

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Cited by

Sorted by citations

Authors
Goldman, A. D., Beatty, J. T., & Landweber, L. F.
Affiliations
  • Oberlin College (US)
  • Princeton University (US)
Corresponding author
  • Goldman, Aaron David
  • Landweber, Laura F.
ORCID
Venue
Journal of Molecular Evolution
Publisher
Springer Science and Business Media LLC
Published
2016-01
Volume
82
Issue
1
Pages
17-26
ISSN
  • 0022-2844 (ISSN-L)
  • 1432-1432
DOI
10.1007/s00239-015-9722-8
PMC
PMC4709378
OpenAlex
W2227950473
Cited by
81
References
4
Citations by year
2026: 4 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 10 · 2021: 12 · 2020: 12 · 2019: 6 · 2018: 11 · 2017: 6 · 2016: 4
FWCI
5.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Molecular Evolution (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation (MRI 1427949)
  • National Institutes of Health (R01 GM109459)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
TIM barrel, triosephosphate isomerase, protein fold evolution, cofactors, nucleotide cofactors, metal cofactors, protein superfamilies, ribozymes
MeSH terms
Archaea, Bacteria, Enzymes, Triose-Phosphate Isomerase, Consensus Sequence, Protein Structure, Secondary, Evolution, Molecular, Gene Duplication, Proteome, Eukaryota

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