Structure and Conservation of Amyloid Spines From the Candida albicans Als5 Adhesin.
| Autor: | Golan N; Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel., Schwartz-Perov S; Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel., Landau M; Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel.; European Molecular Biology Laboratory (EMBL) and Centre for Structural Systems Biology, Hamburg, Germany., Lipke PN; Biology Department, Brooklyn College of the City University of New York, Brooklyn, NY, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in molecular biosciences [Front Mol Biosci] 2022 Jul 06; Vol. 9, pp. 926959. Date of Electronic Publication: 2022 Jul 06 (Print Publication: 2022). |
| DOI: | 10.3389/fmolb.2022.926959 |
| Abstrakt: | Candida Als family adhesins mediate adhesion to biological and abiotic substrates, as well as fungal cell aggregation, fungal-bacterial co-aggregation and biofilm formation. The activity of at least two family members, Als5 and Als1, is dependent on amyloid-like protein aggregation that is initiated by shear force. Each Als adhesin has a ∼300-residue N-terminal Ig-like/invasin region. The following 108-residue, low complexity, threonine-rich (T) domain unfolds under shear force to expose a critical amyloid-forming segment 322 SNGIVIVATTRTV 334 at the interface between the Ig-like/invasin domain 2 and the T domain of C andida albicans Als5. Amyloid prediction programs identified six potential amyloidogenic sequences in the Ig-like/invasin region and three others in the T domain of C. albicans Als5. Peptides derived from four of these sequences formed fibrils that bound thioflavin T, the amyloid indicator dye, and three of these revealed atomic-resolution structures of cross-β spines. These are the first atomic-level structures for fungal adhesins. One of these segments, from the T domain, revealed kinked β-sheets, similarly to LARKS (Low-complexity, Amyloid-like, Reversible, Kinked segments) found in human functional amyloids. Based on the cross-β structures in Als proteins, we use evolutionary arguments to identify functional amyloidogenic sequences in other fungal adhesins, including adhesins from Candida auris . Thus, cross-β structures are often involved in fungal pathogenesis and potentially in antifungal therapy. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Golan, Schwartz-Perov, Landau and Lipke.) |
| Databáze: | MEDLINE |
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