Computational study of the impact of nucleotide variations on highly conserved proteins: In the case of actin

Ha T.T. Duong, Hirofumi Suzuki, Saki Katagiri, Mayu Shibata, Misae Arai, Kei Yura*

*Corresponding author for this work

Research output: Contribution to journalComment/debatepeer-review

Abstract

Sequencing of individual human genomes enables studying relationship among nucleotide variations, amino acid substitutions, effect on protein structures and diseases. Many studies have found general tendencies, for instance, that pathogenic variations tend to be found in the buried regions of the protein structures, that benign variations tend to be found on the surface of the proteins, and that variations on evolutionary conserved residues tend to be pathogenic. These tendencies were deduced from globular proteins with standard evolutionary changes in amino acid sequences. In this study, we investigated the variation distribution on actin, one of the highly conserved proteins. Many nucleotide variations and three-dimensional structures of actin have been registered in databases. By combining those data, we found that variations buried inside the protein were rather benign and variations on the surface of the protein were pathogenic. This idiosyncratic distribution of the variation impact is likely ascribed to the extensive use of the surface of the protein for protein-protein interactions in actin.

Original languageEnglish
Article numbere190025
JournalBiophysics and physicobiology
Volume19
DOIs
Publication statusPublished - 2022

Keywords

  • VUS
  • conservation
  • pathogenic variation
  • protein three-dimensional structure
  • protein-protein interaction

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Physiology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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