A Fifth of the Protein World: Rossmann-like Proteins as an Evolutionarily Successful Structural unit

Kirill E. Medvedev, Lisa N. Kinch, R. Dustin Schaeffer, Jimin Pei, Nick V. Grishin

Research output: Contribution to journalArticlepeer-review

Abstract

The Rossmann-like fold is the most prevalent and diversified doubly-wound superfold of ancient evolutionary origin. Rossmann-like domains are present in a variety of metabolic enzymes and are capable of binding diverse ligands. Discerning evolutionary relationships among these domains is challenging because of their diverse functions and ancient origin. We defined a minimal Rossmann-like structural motif (RLM), identified RLM-containing domains among known 3D structures (20%) and classified them according to their homologous relationships. New classifications were incorporated into our Evolutionary Classification of protein Domains (ECOD) database. We defined 156 homology groups (H-groups), which were further clustered into 123 possible homology groups (X-groups). Our analysis revealed that RLM-containing proteins constitute approximately 15% of the human proteome. We found that disease-causing mutations are more frequent within RLM domains than within non-RLM domains of these proteins, highlighting the importance of RLM-containing proteins for human health.

Original languageEnglish (US)
Article number166788
JournalJournal of Molecular Biology
Volume433
Issue number4
DOIs
StatePublished - Feb 19 2021

Keywords

  • Rossmann-fold
  • domains classification
  • minimal Rossmann-like motif
  • protein evolution

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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