title: Self-assembly of proteins into a three-dimensional multilayer system: investigation of the surface of the human fungal pathogen Aspergillus fumigatus.
abstract: Hydrophobins are small surface active proteins that fulfil a wide spectrum of functions in fungal growth and development. The human fungal pathogen Aspergillus fumigatus expresses RodA hydrophobins that self-assemble on the outer conidial surface into tightly organized nanorods known as rodlets. AFM investigation of the conidial surface allows us to evidence that RodA hydrophobins self-assemble into rodlets through bilayers. Within bilayers, hydrophilic domains of hydrophobins point inward, thus making a hydrophilic core, while hydrophobic domains point outward. AFM measurements reveal that several rodlet bilayers are present on the conidial surface thus showing that proteins self-assemble into a complex three-dimensional multilayer system. The self-assembly of RodA hydrophobins into rodlets results from attractive interactions between stacked β-sheets, which conduct to a final linear cross-β spine structure. A Monte Carlo simulation shows that anisotropic interactions are the main driving forces leading the hydrophobins to self-assemble into parallel rodlets, which are further structured in nanodomains. Taken together, these findings allow us to propose a mechanism, which conducts RodA hydrophobins to a highly ordered rodlet structure. The mechanism of hydrophobin assembly into rodlets offers new prospects for the development of more efficient strategies leading to disruption of rodlet formation allowing a rapid detection of the fungus by the immune system.
authors.affiliation: Institut des Matériaux Jean Rouxel, Université de Nantes, 2 rue de la Houssinière, 44322 Nantes Cedex 3, France.
authors.forename: Agata
authors.initials: A
authors.lastname: Zykwinska
authors.affiliation: Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Universitaire d'Angers, France; UNAM Université, Université d'Angers, Groupe d'Etude des Interactions Hôte-Pathogène, UPRES-EA 3142 Angers, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Pihet
authors.affiliation: IPREM Equipe de Physique et Chimie des Polymères, UMR 5254 CNRS, Université de Pau et des Pays de l'Adour, Hélioparc, 2 Avenue du Président Angot, 64053 Pau Cedex, France.
authors.forename: Sadia
authors.initials: S
authors.lastname: Radji
authors.affiliation: Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Universitaire d'Angers, France; UNAM Université, Université d'Angers, Groupe d'Etude des Interactions Hôte-Pathogène, UPRES-EA 3142 Angers, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Bouchara
authors.affiliation: Institut des Matériaux Jean Rouxel, Université de Nantes, 2 rue de la Houssinière, 44322 Nantes Cedex 3, France. Electronic address: Stephane.Cuenot@cnrs-imn.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Cuenot
mesh_terms: D016880:Anisotropy; D001232:Aspergillus fumigatus / Q000737:chemistry* / Q000472:pathogenicity / Q000648:ultrastructure; D005656:Fungal Proteins / Q000737:chemistry* / Q000648:ultrastructure; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D018625:Microscopy, Atomic Force; D009010:Monte Carlo Method; D043942:Nanotubes; D055503:Protein Multimerization; D013172:Spores, Fungal / Q000737:chemistry* / Q000472:pathogenicity / Q000648:ultrastructure; D013499:Surface Properties
chemical_list: D005656:Fungal Proteins
keywords: Anisotropic interaction; Aspergillus fumigatus; Monte Carlo simulation; RodA hydrophobin; Rodlet; Self-assembly