R432 Is a Key Residue for the Multiple Functions of Ndt80p in Candida Albicans

Cell Mol Life Sci. 2012 Mar;69(6):1011-23. doi: 10.1007/s00018-011-0849-5. Epub 2011 Oct 16.

Abstract

Ndt80p is an important transcription modulator to various stress-response genes in Candida albicans, the most common human fungal pathogen in systemic infections. We found that Ndt80p directly regulated its target genes, such as YHB1, via the mid-sporulation element (MSE). Furthermore, the ndt80(R432A) allele, with a reduced capability to bind MSE, failed to complement the defects caused by null mutations of NDT80. Thus, the R432 residue in the Ndt80p DNA-binding domain is involved in all tested functions, including cell separation, drug resistance, nitric oxide inactivation, germ tube formation, hyphal growth, and virulence. Hence, the importance of the R432 residue suggests a novel approach for designing new antifungal drugs by blocking the interaction between Ndt80p and its targets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Candida albicans / pathogenicity*
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / physiology*
  • Hyphae / growth & development
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / physiology*
  • Virulence

Substances

  • DNA-Binding Proteins
  • Ndt80 protein, Candida albicans
  • Transcription Factors
  • Nitric Oxide
  • DNA