Mutagenesis of tGCN5 core region reveals two critical surface residues F90 and R140

Kinjal Rajesh Mehta, Yan M. Chan, Man X. Lee, Ching Yao Yang, Natalya Voloshchuk, Jin Montclare

Research output: Contribution to journalArticle

Abstract

Tetrahymena General Control Non-Derepressor 5 (tGCN5) is a critical regulator of gene transcription via acetylation of histones. Since the acetylation ability has been attributed to the " core region" , we perform mutagenesis of residues within the tGCN5 " core region" in order to identify those critical for function and stability. Residues that do not participate in catalysis are identified, mutated and characterized for activity, structure and thermodynamic stability. Variants I107V, Q114L, A121T and A130S maintain the acetylation function relative to wild-type tGCN5, while variants F90Y, F112R and R140H completely abolish function. Of the three non-functional variants, since F112 is mutated into a non-homologous charged residue, a loss in function is expected. However, the remaining two variants are mutated into homologous residues, suggesting that F90 and R140 are critical for the activity of tGCN5. While mutation to homologous residue maintains acetylation of histone H3 for the majority of the variants, the two surface-exposed residues, F90 and R140, appear to be essential for tGCN5 function, structure or stability.

Original languageEnglish (US)
Pages (from-to)363-368
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume400
Issue number3
DOIs
StatePublished - Sep 2010

Fingerprint

Tetrahymena
Mutagenesis
Acetylation
Histones
Transcription
Regulator Genes
Catalysis
Thermodynamics
Thermodynamic stability
Thermodynamic properties
Genes
Mutation

Keywords

  • Histone
  • Histone acetyltransferase (HAT)
  • Homology
  • Structural stability
  • TGCN5
  • Thermodynamic stability

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Mutagenesis of tGCN5 core region reveals two critical surface residues F90 and R140. / Mehta, Kinjal Rajesh; Chan, Yan M.; Lee, Man X.; Yang, Ching Yao; Voloshchuk, Natalya; Montclare, Jin.

In: Biochemical and Biophysical Research Communications, Vol. 400, No. 3, 09.2010, p. 363-368.

Research output: Contribution to journalArticle

Mehta, Kinjal Rajesh ; Chan, Yan M. ; Lee, Man X. ; Yang, Ching Yao ; Voloshchuk, Natalya ; Montclare, Jin. / Mutagenesis of tGCN5 core region reveals two critical surface residues F90 and R140. In: Biochemical and Biophysical Research Communications. 2010 ; Vol. 400, No. 3. pp. 363-368.
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