Fast slow folding of an outer membrane porin.

In comparison to globular proteins, the spontaneous folding and insertion of ß-barrel membrane proteins are surprisingly slow, typically occurring on the order of minutes. Using single-molecule Förster resonance energy transfer to report on the folding of fluorescently labeled outer membrane protein G we measured the real-time insertion of a ß-barrel membrane protein from an unfolded state. Folding events were rare and fast (<20 ms), occurring immediately upon arrival at the membrane. This combination of infrequent, but rapid, folding resolves this apparent dichotomy between slow ensemble kinetics and the typical timescales of biomolecular folding.