期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 9, 页码 2490-2495出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1522946113
关键词
bacterial adhesion; mechanical stability; single-molecule force spectroscopy; Gram-positive pili; isopeptide bond
资金
- NIH [HL66030, HL61228, AI106072]
- National Institute of Dental and Craniofacial Research [DE017382, DE025015]
- Marie Curie International Incoming Fellowship [FP7-PEOPLE-2010-COFUND-267149]
- Div Of Biological Infrastructure
- Direct For Biological Sciences [1252857] Funding Source: National Science Foundation
Pathogenic bacteria adhere despite severe mechanical perturbations induced by the host, such as coughing. In Gram-positive bacteria, extracellular protein appendages termed pili are necessary for adherence under mechanical stress. However, little is known about the behavior of Gram-positive pili under force. Here, we demonstrate a mechanism by which Gram-positive pili are able to dissipate mechanical energy through mechanical unfolding and refolding of isopeptide bond-delimited polypeptide loops present in Ig-type CnaA domains. Using single-molecule force spectroscopy, we find that these loops of the pilus subunit SpaA of the SpaA-type pilus from Corynebacterium diphtheriae and FimA of the type 2 pilus from Actinomyces oris unfold and extend at forces that are the highest yet reported for globular proteins. Loop refolding is limited by the hydrophobic collapse of the polypeptide and occurs in milliseconds. Remarkably, both SpaA and FimA initially refold to mechanically weaker intermediates that recover strength with time or ligand binding. Based on the high force extensibility, CnaA-containing pili can dissipate similar to 28-fold as much energy compared with their inextensible counterparts before reaching forces sufficient to cleave covalent bonds. We propose that efficient mechanical energy dissipation is key for sustained bacterial attachment against mechanical perturbations.
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