NDLI: Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in Pseudomonas aeruginosa Biofilms

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Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in Pseudomonas aeruginosa Biofilms

Content Provider	Scilit
Author	Bleem, Alissa Christiansen, Gunna Madsen, Daniel J. Maric, Hans Strømgaard, Kristian Bryers, James D. Daggett, Valerie Meyer, Rikke L. Otzen, Daniel E.
Copyright Year	2018
Description	Journal: Journal of Molecular Biology Amyloids are typically associated with neurodegenerative diseases, but recent research demonstrates that several bacteria utilize functional amyloid fibrils to fortify the biofilm extracellular matrix and thereby resist antibiotic treatments. In Pseudomonas aeruginosa, these fibrils are composed predominantly of FapC, a protein with high-sequence conservation among the genera. Previous studies established FapC as the major amyloid subunit, but its mechanism of fibril formation in P. aeruginosa remained largely unexplored. Here, we examine the FapC sequence in greater detail through a combination of bioinformatics and protein engineering, and we identify specific motifs that are implicated in amyloid formation. Sequence regions of high evolutionary conservation tend to coincide with regions of high amyloid propensity, and mutation of amyloidogenic motifs to a designed, non-amyloidogenic motif suppresses fibril formation in a pH-dependent manner. We establish the particular significance of the third repeat motif in promoting fibril formation and also demonstrate emergence of soluble oligomer species early in the aggregation pathway. The insights reported here expand our understanding of the mechanism of amyloid polymerization in P. aeruginosa, laying the foundation for development of new amyloid inhibitors to combat recalcitrant biofilm infections.
Related Links	http://europepmc.org/articles/pmc6178955?pdf=render https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178955/pdf
Ending Page	3763
Page Count	13
Starting Page	3751
ISSN	00222836
e-ISSN	10898638
DOI	10.1016/j.jmb.2018.06.043
Journal	Journal of Molecular Biology
Issue Number	20
Volume Number	430
Language	English
Publisher	Elsevier BV
Publisher Date	2018-06-30
Access Restriction	Open
Subject Keyword	Journal: Journal of Molecular Biology Biochemistry and Molecular Biology Protein Aggregation Bacterial Amyloid Extracellular Matrix Protein Sequence Analysis Peptide Microarray
Content Type	Text
Resource Type	Article
Subject	Structural Biology Molecular Biology Biophysics

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