Protein dynamics analysis reveals that missense mutations in cancer-related genes appear frequently on hinge-neighboring residues

Jan Fehmi Sayılgan, Türkan Haliloğlu, Mehmet Gönen

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Missense mutations have various effects on protein structures, also leading to distorted protein dynamics that plausibly affects the function. We hypothesized that missense mutations in cancer-related genes selectively target hinge-neighboring residues that orchestrate collective structural dynamics. To test our hypothesis, we selected 69 cancer-related genes from the Cancer Gene Census database and their representative protein structures from the Protein Data Bank. We first identified the hinge residues in two global modes of motion by applying the Gaussian Network Model. We then showed that missense mutations are significantly enriched on hinge-neighboring residues in oncogenes and tumor suppressor genes. We observed that several oncogenes (eg, MAP2K1, PTPN11, and KRAS) and tumor suppressor genes (eg, EZH2, CDKN2C, and RHOA) strongly exhibit this phenomenon. This study highlights and rationalizes the functional importance of missense mutations on hinge-neighboring residues in cancer.

Original languageEnglish (US)
Pages (from-to)512-519
Number of pages8
JournalProteins: Structure, Function and Bioinformatics
Volume87
Issue number6
DOIs
StatePublished - Jun 2019

Keywords

  • cancer
  • hinge residues
  • missense mutation
  • protein dynamics

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Fingerprint Dive into the research topics of 'Protein dynamics analysis reveals that missense mutations in cancer-related genes appear frequently on hinge-neighboring residues'. Together they form a unique fingerprint.

Cite this