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

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Jan Fehmi Sayılgan1, Türkan Haliloğlu2,3, Mehmet Gönen4,5,6

  • 1Graduate School of Sciences and Engineering, Koç University, İstanbul, Turkey.

Proteins
|February 21, 2019
PubMed

Insights

Missense mutations in cancer genes often affect hinge-neighboring residues critical for protein dynamics and function. This study reveals a significant enrichment of these mutations in key cancer-related genes.

Area of Science:

  • Structural biology
  • Cancer genomics
  • Protein dynamics

Background:

  • Missense mutations can alter protein structure and dynamics, potentially impacting cellular function.
  • Understanding mutation patterns in cancer-related genes is crucial for identifying disease mechanisms.

Purpose of the Study:

  • To investigate whether missense mutations in cancer-related genes preferentially occur at hinge-neighboring residues.
  • To explore the role of these residues in orchestrating collective protein structural dynamics.

Main Methods:

  • Selected 69 cancer-related genes and their protein structures from the Cancer Gene Census and Protein Data Bank.
  • Utilized the Gaussian Network Model to identify hinge residues in global protein motion modes.
  • Analyzed the distribution of missense mutations relative to identified hinge residues.

Main Results:

  • Demonstrated a significant enrichment of missense mutations on hinge-neighboring residues in both oncogenes and tumor suppressor genes.
  • Observed this phenomenon in specific genes, including MAP2K1, PTPN11, KRAS, EZH2, CDKN2C, and RHOA.

Conclusions:

  • Missense mutations in cancer genes frequently target hinge-neighboring residues.
  • These findings highlight the functional significance of mutations affecting protein dynamics in cancer development.
Keywords:
cancerhinge residuesmissense mutationprotein dynamics

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