Evidence for the emergence of β-trefoils by 'Peptide Budding' from an IgG-like β-sandwich

Liam M. Longo, Rachel Kolodny, Shawn E. McGlynn

Research output: Contribution to journalArticlepeer-review

Abstract

As sequence and structure comparison algorithms gain sensitivity, the intrinsic interconnectedness of the protein universe has become increasingly apparent. Despite this general trend, β-trefoils have emerged as an uncommon counterexample: They are an isolated protein lineage for which few, if any, sequence or structure associations to other lineages have been identified. If β-trefoils are, in fact, remote islands in sequence-structure space, it implies that the oligomerizing peptide that founded the β-trefoil lineage itself arose de novo. To better understand β-trefoil evolution, and to probe the limits of fragment sharing across the protein universe, we identified both 'β-trefoil bridging themes' (evolutionarily-related sequence segments) and 'β-trefoil-like motifs' (structure motifs with a hallmark feature of the β-trefoil architecture) in multiple, ostensibly unrelated, protein lineages. The success of the present approach stems, in part, from considering β-trefoil sequence segments or structure motifs rather than the β-trefoil architecture as a whole, as has been done previously. The newly uncovered inter-lineage connections presented here suggest a novel hypothesis about the origins of the β-trefoil fold itself-namely, that it is a derived fold formed by 'budding' from an Immunoglobulin-like β-sandwich protein. These results demonstrate how the evolution of a folded domain from a peptide need not be a signature of antiquity and underpin an emerging truth: Few protein lineages escape nature's sewing table.

Original languageEnglish
Article numbere1009833
JournalPLoS Computational Biology
Volume18
Issue number2
DOIs
StatePublished - Feb 2022

Bibliographical note

Publisher Copyright:
© 2022 Longo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Ecology
  • Modeling and Simulation
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

Fingerprint

Dive into the research topics of 'Evidence for the emergence of β-trefoils by 'Peptide Budding' from an IgG-like β-sandwich'. Together they form a unique fingerprint.

Cite this