Gatekeeper residues in the major curlin subunit modulate bacterial amyloid fiber biogenesis

Xuan Wang, Yizhou Zhou, Juan Jie Ren, Neal D. Hammer, Matthew R. Chapman

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Amyloid fibers are filamentous protein structures commonly associated with neurodegenerative diseases. Unlike disease-associated amyloids, which are the products of protein misfolding, Escherichia coli assemble membrane-anchored functional amyloid fibers called curli. Curli fibers are composed of two proteins, CsgA and CsgB. In vivo, the polymerization of the major curli subunit protein, CsgA, is dependent on CsgB-mediated nucleation. The amyloid core of CsgA features five imperfect repeats (R1-R5), and R1 and R5 govern CsgA responsiveness to CsgB nucleation and self-seeding by CsgA fibers. Here, the specificity of bacterial amyloid nucleation was probed, revealing that certain aspartic acid and glycine residues inhibit the intrinsic aggregation propensities and nucleation responsiveness of R2, R3, and R4. These residues function as "gatekeepers" to modulate CsgA polymerization efficiency and potential toxicity. A CsgA molecule lacking gatekeeper residues polymerized in vitro signifi-cantly faster than wild-type CsgA and polymerized in vivo in the absence of the nucleation machinery, resulting in mislocalized fi-bers. This uncontrolled polymerizationwasassociated with cytotoxicity, suggesting that incorrectly regulated CsgA polymerization was detrimental to the cell.

Original languageEnglish (US)
Pages (from-to)163-168
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number1
DOIs
StatePublished - 2010
Externally publishedYes

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Amyloid
Polymerization
Escherichia coli Proteins
Protein Subunits
Aspartic Acid
Neurodegenerative Diseases
Glycine
Proteins
Membranes

Keywords

  • Amyloid
  • Curli
  • Escherichia coli
  • Nucleation
  • Protein aggregation

ASJC Scopus subject areas

  • General

Cite this

Gatekeeper residues in the major curlin subunit modulate bacterial amyloid fiber biogenesis. / Wang, Xuan; Zhou, Yizhou; Ren, Juan Jie; Hammer, Neal D.; Chapman, Matthew R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 1, 2010, p. 163-168.

Research output: Contribution to journalArticle

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