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Solution structure and novel insights into phylogeny and mode of action of the Neosartorya (Aspergillus) fischeri antifungal protein (NFAP)
- Publication Year :
- 2019
-
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.
- Subjects :
- Models, Molecular
Cytoplasm
Protein Conformation
In silico
Neosartorya
Antifungal drug
02 engineering and technology
Biochemistry
Neurospora crassa
Fungal Proteins
03 medical and health sciences
Természettudományok
Structural Biology
Amino Acid Sequence
Mode of action
Kémiai tudományok
Molecular Biology
Phylogeny
030304 developmental biology
0303 health sciences
Aspergillus
Sequence Homology, Amino Acid
biology
General Medicine
021001 nanoscience & nanotechnology
biology.organism_classification
Protein tertiary structure
Solutions
Protein Transport
Penicillium
0210 nano-technology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....b816f9fe2ea2ae862728730abc3f3e37