Force-dependent polymorphism in type IV pili reveals hidden epitopes

Nicolas Biais, Dustin L. Higashi, Jasna Brujić, Magdalene So, Michael P. Sheetz

    Research output: Contribution to journalArticlepeer-review


    Through evolution, nature has produced exquisite nanometric structures, with features unrealized in the most advanced manmade devices. Type IV pili (Tfp) represent such a structure: 6-nmwide retractable filamentous appendages found in many bacteria, including human pathogens. Whereas the structure of Neisseria gonorrhoeae Tfp has been defined by conventional structural techniques, it remains difficult to explain the wide spectrum of functions associated with Tfp. Here we uncover a previously undescribed force-induced quaternary structure of the N. gonorrhoeae Tfp. By using a combination of optical and magnetic tweezers, atomic force microscopy, and molecular combing to apply forces on purified Tfp, we demonstrate that Tfp subjected to approximately 100 pN of force will transition into a new conformation. The new structure is roughly 3 times longer and 40% narrower than the original structure. Upon release of the force, the Tfp fiber regains its original form, indicating a reversible transition. Equally important, we show that the force-induced conformation exposes hidden epitopes previously buried in the Tfp fiber. We postulate that this transition provides a means for N. gonorrhoeae to maintain attachment to its host while withstanding intermittent forces encountered in the environment. Our findings demonstrate the need to reassess our understanding of Tfp dynamics and functions. They could also explain the structural diversity of other helical polymers while presenting a unique mechanism for polymer elongation and exemplifying the extreme structural plasticity of biological polymers.

    Original languageEnglish (US)
    Pages (from-to)11358-11363
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Issue number25
    StatePublished - Jun 22 2010


    • Alternate immunogenic properties
    • Force polymorphism

    ASJC Scopus subject areas

    • General


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