Solution structure and novel insights into phylogeny and mode of action of the Neosartorya (Aspergillus) fischeri antifungal protein (NFAP)

Dorottya Hajdu, Anna Huber, András Czajlik, Liliána Tóth, Z. Kele, S. Kocsubé, Ádám Fizil, Florentine Marx, László Galgóczy, G. Batta

Research output: Contribution to journalArticle

Abstract

Small, cysteine-rich and cationic antifungal proteins from natural sources are promising candidates for the development of novel treatment strategies to prevent and combat infections caused by drug-resistant fungi. However, limited information about their structure and antifungal mechanism hampers their future applications. In the present study, we determined the solution structure, dynamics and associated solvent areas of the Neosartorya (Aspergillus) fischeri antifungal protein NFAP. Genome mining within the genus revealed the presence of orthologous genes in N. fischeri and Neosartorya spathulata, and genes encoding closely related proteins can be found in Penicillium brasiliensis and Penicillium oxalicum. We show that the tertiary structure of these putative proteins can be resolved using the structure of NFAP as reliable template for in silico prediction. Localization studies with fluorescence-labelled protein pointed at an energy-dependent uptake mechanism of NFAP in the sensitive model fungus Neurospora crassa and subsequent cytoplasmic localization coincided with cell-death induction. The presented results contribute to a better understanding of the structure/function relationship of NFAP and related proteins and pave the way towards future antifungal drug development.

Original languageEnglish
Pages (from-to)511-522
Number of pages12
JournalInternational Journal of Biological Macromolecules
Volume129
DOIs
Publication statusPublished - May 15 2019

Fingerprint

Neosartorya
Aspergillus
Phylogeny
Penicillium
Proteins
Fungi
Neurospora crassa
Genes
Tertiary Protein Structure
Pharmaceutical Preparations
Computer Simulation
Cysteine
Gene encoding
Cell Death
Fluorescence
Genome
Cell death
Aspergillus antifungal protein
N-formyl-1-aminopyrene
Infection

Keywords

  • Antifungal mechanism
  • Neosartorya (Aspergillus) fischeri antifungal protein (NFAP)
  • Nuclear magnetic resonance (NMR)

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Cite this

Solution structure and novel insights into phylogeny and mode of action of the Neosartorya (Aspergillus) fischeri antifungal protein (NFAP). / Hajdu, Dorottya; Huber, Anna; Czajlik, András; Tóth, Liliána; Kele, Z.; Kocsubé, S.; Fizil, Ádám; Marx, Florentine; Galgóczy, László; Batta, G.

In: International Journal of Biological Macromolecules, Vol. 129, 15.05.2019, p. 511-522.

Research output: Contribution to journalArticle

Hajdu, Dorottya ; Huber, Anna ; Czajlik, András ; Tóth, Liliána ; Kele, Z. ; Kocsubé, S. ; Fizil, Ádám ; Marx, Florentine ; Galgóczy, László ; Batta, G. / Solution structure and novel insights into phylogeny and mode of action of the Neosartorya (Aspergillus) fischeri antifungal protein (NFAP). In: International Journal of Biological Macromolecules. 2019 ; Vol. 129. pp. 511-522.
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