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A DNA‐promoted amyloid proteinopathy in Escherichia coli
Author(s) -
FernándezTresguerres M. Elena,
MorenoDíaz de la Espina Susana,
GassetRosa Fátima,
Giraldo Rafael
Publication year - 2010
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2010.07299.x
Subject(s) - biology , nucleoid , amyloid (mycology) , escherichia coli , dna , cytokinesis , amyloid disease , biochemistry , microbiology and biotechnology , cell division , cell , amyloid fibril , gene , medicine , botany , disease , pathology , amyloid β
Summary Protein amyloids arise from the conformational conversion and assembly of a soluble protein into fibrilar aggregates with a crossed β‐sheet backbone. Amyloid aggregates are able to replicate by acting as a template for the structural transformation and accretion of further protein molecules. In physicochemical terms, amyloids arguably constitute the simplest self‐replicative macromolecular assemblies. Similarly to the mammalian proteins PrP and α‐synuclein, the winged‐helix dimerization (WH1) domain of the bacterial, plasmid‐encoded protein RepA can assemble into amyloid fibres upon binding to DNA in vitro . Here we report that a hyper‐amyloidogenic functional variant (A31V) of RepA, fused to a red fluorescent protein, causes an amyloid proteinopathy in Escherichia coli with the following features: (i) in the presence of multiple copies of the specific DNA sequence opsp , WH1(A31V) accumulates as cytoplasmatic inclusions segregated from the nucleoid; (ii) such aggregates are amyloid in nature; (iii) bacteria carrying the amyloid inclusions age , exhibiting a fivefold expanded generation time; (iv) before cytokinesis, small inclusions are assembled de novo and transferred to the daughter cells, in which transmission failures cure amyloidosis; and (v) in the absence of inducer DNA, purified cellular WH1(A31V) inclusions seed amyloid fibre growth in vitro from the soluble protein. RepA‐WH1 is a suitable bacterial model system for amyloid proteinopathies.