AI Article Synopsis
- Coupled folding-binding is crucial for the function of many disordered proteins but remains poorly understood, prompting the study of free-energy landscapes in interacting protein sequences.
- The research examines two specific sequences that can form a stable structure at low temperatures, exploring different binding mechanisms that significant influence their interaction.
- Adding disordered segments to the sequences can lower the energy barrier for binding, making the interaction easier, even if these segments don't significantly affect the overall stability.
Article Abstract
Coupled folding-binding is central to the function of many intrinsically disordered proteins, yet not fully understood. With a continuous three-letter protein model, we explore the free-energy landscape of pairs of interacting sequences and how it is impacted by 1), variations in the binding mechanism; and 2), the addition of disordered flanks to the binding region. In particular, we focus on two sequences, one with 16 and one with 35 amino acids, which make a stable dimeric three-helix bundle at low temperatures. Three distinct binding mechanisms are realized by altering the stabilities of the individual monomers: docking, coupled folding-binding of a single α-helix, and synergistic folding and binding. Compared to docking, the free-energy barrier for binding is reduced when the single α-helix is allowed to fold upon binding, but only marginally. A greater reduction is found for synergistic folding, which in addition results in a binding transition state characterized by very few interchain contacts. Disordered flanking chain segments attached to the α-helix sequence can, despite a negligible impact on the dimer stability, lead to a downhill free-energy surface in which the barrier for binding is eliminated.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3274785 | PMC |
| http://dx.doi.org/10.1016/j.bpj.2011.12.008 | DOI Listing |
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