Fast slow folding of an Outer Membrane Porin

In comparison to globular proteins, the spontaneous folding and insertion of {beta}-barrel membrane proteins is surprisingly slow, typically occurring on the order of minutes. Using single-molecule Forster Resonance Energy Transfer to report on the folding of fluorescently-labelled Outer Membrane Protein G we measured the real-time insertion of a {beta}-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 rare, folding resolves this apparent dichotomy between slow ensemble kinetics, and the typical timescales of biomolecular folding.