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[Perspective] Membrane proteins scrambling through a folding landscape

Single-molecule force spectroscopy (SMFS) (1) measures the extension of a molecule when subjected to force. The folding of a protein can be explored by pulling on one terminus to unfold it; upon relaxation, it may refold toward its native states (2, 3). Transmembrane proteins typically unfold stepwise as structural segments (which can consist of parts of single or multiple secondary structures) are extracted from the membrane (see the figure, top panel) (4). Once extracted, the unfolded segment can insert back into the membrane and fold toward the native protein structure…

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