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

Autor: Hajdu D; Department of Organic Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary., Huber A; Division of Molecular Biology, Biocenter, Medical University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, Austria., Czajlik A; Department of Organic Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary., Tóth L; Institute of Plant Biology, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, H-6726 Szeged, Hungary; Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary., Kele Z; Department of Medical Chemistry, Faculty of Medicine, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary., Kocsubé S; Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary., Fizil Á; Department of Organic Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary., Marx F; Division of Molecular Biology, Biocenter, Medical University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, Austria., Galgóczy L; Division of Molecular Biology, Biocenter, Medical University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, Austria; Institute of Plant Biology, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, H-6726 Szeged, Hungary; Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary. Electronic address: galgoczi.laszlo@brc.mta.hu., Batta G; Department of Organic Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary; Department of Organic Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary. Electronic address: batta@unideb.hu.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2019 May 15; Vol. 129, pp. 511-522. Date of Electronic Publication: 2019 Feb 07.
DOI: 10.1016/j.ijbiomac.2019.02.016
Abstrakt: 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.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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