Thermodynamics of Folding, Stabilization, and Binding in an Engineered Protein−Protein Complex
Copyright policy )Thermodynamics of Folding, Stabilization, and Binding in an Engineered Protein−Protein Complex
We analyzed the thermodynamics of a complex protein-protein binding interaction using the (engineered) Z(SPA)(-)(1) affibody and it's Z domain binding partner as a model. Free Z(SPA)(-)(1) exists in an equilibrium between a molten-globule-like (MG) state and a completely unfolded state, wheras a well-ordered structure is observed in the Z:Z(SPA)(-)(1) complex. The thermodynamics of the MG state unfolding equilibrium can be separated from the thermodynamics of binding and stabilization by combined analysis of isothermal titration calorimetry data and a separate van't Hoff analysis of thermal unfolding. We find that (i) the unfolding equilibrium of free Z(SPA)(-)(1) has only a small influence on effective binding affinity, that (ii) the Z:Z(SPA)(-)(1) interface is inconspicuous and structure-based energetics calculations suggest that it should be capable of supporting strong binding, but that (iii) the conformational stabilization of the MG state to a well-ordered structure in the Z:Z(SPA)(-)(1) complex is associated with a large change in conformational entropy that opposes binding.
- University of Gothenburg Sweden
- Royal Institute of Technology Sweden
Models, Molecular, Kinetics, Protein Folding, Structure-Activity Relationship, Protein Conformation, Thermodynamics, Carrier Proteins, Protein Engineering, Protein Binding, Protein Structure, Tertiary
Models, Molecular, Kinetics, Protein Folding, Structure-Activity Relationship, Protein Conformation, Thermodynamics, Carrier Proteins, Protein Engineering, Protein Binding, Protein Structure, Tertiary
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).27 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!