Binding mechanism of a de novo coiled coil complex elucidated from surface forces measurements

We used the Surface Forces Apparatus to elucidate the interaction mechanism between grafted 5 heptad-long peptides engineered to spontaneously form a heterodimeric coiled-coil complex. The results demonstrated that when intimate contact between peptides is reached, binding occurs first via weakly interacting but more mobile distal heptads, suggesting an induced-fit association process. Precise control of the distance between peptide-coated surfaces allowed to quantitatively monitor the evolution of their biding energy. The binding energy of the coiled-coil complex increased in a stepwise fashion rather than monotonically with the overlapping distance, each step corresponding to the interaction between a quantized number of heptads. Surface forces data were corroborated to surface plasmon resonance measurements and molecular dynamics simulations and allowed the calculation of the energetic contribution of each heptad within the coiled-coil complex. (C) 2020 Elsevier Inc. All rights reserved.

Automated summary

This study utilized the Surface Forces Apparatus to investigate the interaction mechanism between specific peptides forming a helical structure, revealing that binding initiates with weak interactions of distal heptads followed by an induced-fit process. Precise control of the distance between peptide-coated surfaces enabled quantitative monitoring of the evolution of binding energy.