TY - JOUR SP - Azonosító: 183246 AV - public EP - Terjedelem: 14 p UR - http://doi.org/10.1016/j.bbamem.2020.183246 A1 - Huber Anna A1 - Galgóczi László Norbert A1 - Váradi Györgyi A1 - Holzknecht Jeanett A1 - Kakar A. A1 - Malanovic Nermina A1 - Leber Regina A1 - Koch Jakob A1 - Keller Markus Andreas A1 - Batta Gyula A1 - Tóth Gábor A1 - Marx Florentine SN - 0005-2736 IS - 8 VL - 1862 TI - Two small, cysteine-rich and cationic antifungal proteins from Penicillium chrysogenum : A comparative study of PAF and PAFB ID - publicatio19541 N1 - Funding Agency and Grant Number: Hungarian National Research, Development and Innovation (NKFI) Office [ANN 131341, GINOP-2.3.2-15-2016-00014, 20391-3/2018/FEKUSTRAT]; New National Excellence Program of the Ministry for Innovation and Technology [UNKP-19-4]; Janos Bolyai Research Scholarship of the Hungarian Academy of SciencesHungarian Academy of Sciences; European Regional Development FundEuropean Union (EU) [GINOP-2.3.2-15-2016-00008, GINOP-2.3.3-15-2016-00004]; Ministry for Innovation and Technology (ITM) [TUDFO/47138-1/2019-ITM FIKP]; Austrian Science FundAustrian Science Fund (FWF) [FWF P25894-B20, I1644-B20, I3132-B21]; EUEuropean Union (EU); [PD 131340] Funding text: The authors want to thank Karl Lohner for the helpful discussion and Sandor Kocsube for advices in the phylogenetic analysis. Research has been funded to F.M. by the Austrian Science Fund (FWF P25894-B20, I1644-B20, I3132-B21), and to L.G. by the Postdoctoral Excellence Program (PD 131340), the bilateral Austrian-Hungarian Joint Research Project (ANN 131341) of the Hungarian National Research, Development and Innovation (NKFI) Office. Present work of L.G. is supported by UNKP-19-4 New National Excellence Program of the Ministry for Innovation and Technology. L.G. has been supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences. Structural research was supported by the EU and co-financed by the European Regional Development Fund under the projects GINOP-2.3.2-15-2016-00008 to G.B. and GINOP-2.3.3-15-2016-00004 (access to 700 MHz NMR facilities). Synthetic work was supported by GINOP-2.3.2-15-2016-00014 and 20391-3/2018/FEKUSTRAT of the Hungarian National Research, Development and Innovation (NKFI) Office, and by TUDFO/47138-1/2019-ITM FIKP of the Ministry for Innovation and Technology (ITM). Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck, 6020, Austria Institute of Plant Biology, Biological Research Centre, Szeged, 6726, Hungary Department of Biotechnology, Faculty of Science and Informatics, University of Szeged, Szeged, 6726, Hungary Department of Medical Chemistry, Faculty of Medicine, University of Szeged, Szeged, 6720, Hungary Institute of Molecular Biosciences, Biophysics Division, University of Graz, Graz, Austria Institute of Human Genetics, Medical University of Innsbruck, Austria Department of Organic Chemistry, Faculty of Science and Technology, University of Debrecen, Debrecen, 4032, Hungary MTA-SZTE Biomimetic Systems Research Group, University of Szeged, Szeged, 6720, Hungary Export Date: 16 July 2020 CODEN: BBBMB Correspondence Address: Marx, F.; Institute of Molecular Biology, Biocenter, Medical University of InnsbruckAustria; email: florentine.marx@i-med.ac.at JF - BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES N2 - The filamentous fungus Penicillium chrysogenum Q176 secretes the antimicrobial proteins (AMPs) PAF and PAFB, which share a compact disulfide-bond mediated, ?-fold structure rendering them highly stable. These two AMPs effectively inhibit the growth of human pathogenic fungi in micromolar concentrations and exhibit antiviral potential without causing cytotoxic effects on mammalian cells in vitro and in vivo. The antifungal mechanism of action of both AMPs is closely linked to - but not solely dependent on - the lipid composition of the fungal cell membrane and requires a strictly regulated protein uptake into the cell, indicating that PAF and PAFB are not canonical membrane active proteins. Variations in their antifungal spectrum and their killing dynamics point towards a divergent mode of action related to their physicochemical properties and surface charge distribution. In this review, we relate characteristic features of PAF and PAFB to the current knowledge about other AMPs of different sources. In addition, we present original data that have never been published before to substantiate our assumptions and provide evidences that help to explain and understand better the mechanistic function of PAF and PAFB. Finally, we underline the promising potential of PAF and PAFB as future antifungal therapeutics. Y1 - 2020/// ER -