title: Curli provide the template for understanding controlled amyloid propagation.
abstract: The uncontrolled formation of amyloid fibers is the hallmark of more than twenty human diseases. In contrast to disease-associated amyloids, which are the products of protein misfolding, E. coli assembles functional amyloid fibers called curli on its surface using an elegant biogenesis machine. Composed of a major subunit, CsgA, and a minor subunit, CsgB, curli play important roles in host cell adhesion, long-term survival and other bacterial community behaviors. Assembly of curli fibers is a template-directed conversion process where membrane-tethered CsgB initiates CsgA polymerization. The CsgA amyloid core is composed of five imperfect repeating units. In a series of in vivo and in vitro experiments, we determined the sequence and structural determinants that guide the initiation and propagation of CsgA polymers. The CsgA N- and C-terminal repeating units govern its polymerization and responsiveness to CsgB. Specifically, conserved glutamine and asparagine residues present in the CsgA N- and C-terminal repeating units are required for CsgB-mediated nucleation and efficient self-assembly.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Chapman
mesh_terms: D000682:Amyloid / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017510:Protein Folding; D020836:Protein Structure, Quaternary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology
chemical_list: D000682:Amyloid; D001426:Bacterial Proteins; C109182:CsgB protein, E coli; D029968:Escherichia coli Proteins; C489688:csgA protein, E coli; C077481:Crl protein, Bacteria