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Issue 42, 2017
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Interplay between the folding mechanism and binding modes in folding coupled to binding processes

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Abstract

Proteins that fold upon binding to their partners exhibit complex binding behavior such as induced-fit. But the connections between the folding mechanism and the binding mode remain unknown. Here we focus on the high affinity complex between the physiologically and marginally unstable, fast folder PSBD and the E1 subunit of pyruvate dehydrogenase. Using coarse-grained simulations we investigate the binding to E1 of a partially disordered PSBD under two folding scenarios: two-state and downhill. Our simulations show that induced-fit binding requires that PSBD folds–unfolds in the downhill folding regime. In contrast, a two-state folding PSBD must fold completely before it binds. The reason is that effective coupling between folding and binding involves partially folded conformations, which are only sufficiently populated under the downhill folding regime. Our results establish a direct mechanistic link between complex binding and downhill folding, supporting the idea that PSBD operates functionally as a conformational rheostat.

Graphical abstract: Interplay between the folding mechanism and binding modes in folding coupled to binding processes

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Publication details

The article was received on 14 Jul 2017, accepted on 12 Sep 2017 and first published on 18 Oct 2017


Article type: Communication
DOI: 10.1039/C7CP04748G
Citation: Phys. Chem. Chem. Phys., 2017,19, 28512-28516
  • Open access: Creative Commons BY license
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    Interplay between the folding mechanism and binding modes in folding coupled to binding processes

    R. Sharma, D. De Sancho and V. Muñoz, Phys. Chem. Chem. Phys., 2017, 19, 28512
    DOI: 10.1039/C7CP04748G

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