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Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
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Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

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Proteins of generalist and specialist pathogens differ in their amino acid composition

Luz P Blanco1, Bryan L Payne2, Felix Feyertag2

  • 1Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.

Life Science Alliance
|November 21, 2018
PubMed

Insights

Generalist pathogens, which infect many hosts, have more primitive amino acids and disordered regions in their secreted proteins than specialist pathogens. This molecular feature may explain their broader host range.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Evolutionary Biology

Background:

  • Pathogens exhibit varying host specificities, ranging from specialists infecting one host to generalists with a wide host range.
  • The molecular factors governing pathogen host range are not well understood.
  • Generalist pathogens' secreted proteins are hypothesized to possess greater intermolecular interaction capabilities (promiscuity) than those of specialists.

Purpose of the Study:

  • To investigate the molecular determinants of pathogen host range.
  • To test the hypothesis that generalist pathogens have increased primitive amino acid content and intrinsically disordered regions in their proteins, particularly secreted proteins, contributing to their broader host specificity.

Main Methods:

  • Quantified the proportion of primitive amino acids and the percentage of intrinsically disordered residues.
  • Analyzed secreted, membrane, and cytoplasmic proteins from pathogens with differing host specificities.
  • Compared protein features between generalist and specialist pathogens.

Main Results:

  • Found a significant enrichment of primitive amino acids and intrinsically disordered regions in proteins from generalist pathogens compared to specialists.
  • This enrichment was particularly pronounced in secreted proteins of prokaryotic generalists.
  • Results support the hypothesis linking protein composition and disorder to host range.

Conclusions:

  • The amino acid composition and intrinsically disordered content of secreted proteins play a role in determining pathogen host range.
  • These molecular features may enhance protein flexibility and intermolecular interactions, facilitating broader host adaptation in generalist pathogens.

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