Observing folding pathways and kinetics of a single sodium-proton antiporter from Escherichia coli

Alexej Kedrov, Harald Janovjak, Christine Ziegler, Werner Kuhlbrandt, Daniel J. Muller

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36 Citations (Scopus)


Mechanisms of folding and misfolding of membrane proteins are of interest in cell biology. Recently, we have established single-molecule force spectroscopy to observe directly the stepwise folding of the Na +/H+ antiporter NhaA from Escherichia coli in vitro. Here, we improved this approach significantly to track the folding intermediates of a single NhaA polypeptide forming structural segments such as the Na +-binding site, transmembrane α-helices, and helical pairs. The folding rates of structural segments ranged from 0.31 s-1 to 47 s-1, providing detailed insight into a distinct folding hierarchy of an unfolded polypeptide into the native membrane protein structure. In some cases, however, the folding chain formed stable and kinetically trapped non-native structures, which could be assigned to misfolding events of the antiporter.

Original languageEnglish
Pages (from-to)2-8
Number of pages7
JournalJournal of Molecular Biology
Issue number1
Publication statusPublished - 6 Jan 2006
Externally publishedYes


  • Atomic force microscopy
  • Folding kinetics
  • Molecular interactions
  • Single-molecule force spectroscopy
  • Sodium/proton antiporter

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