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Start Over Author "Jakob Dogan" Journal journal of the american chemical society
2 results on '"Jakob Dogan"'

1. Thermodynamics of Folding, Stabilization, and Binding in an Engineered Protein−Protein Complex

Author

Elisabet Wahlberg, Torleif Härd, Jakob Dogan, Vildan Dincbas-Renqvist, and Christofer Lendel

Subjects
Models, Molecular, Isothermal microcalorimetry, Protein Folding, Protein Conformation, Chemistry, Thermodynamics, Isothermal titration calorimetry, General Chemistry, Plasma protein binding, Protein engineering, Protein Engineering, Biochemistry, Catalysis, Protein Structure, Tertiary, Kinetics, Structure-Activity Relationship, Colloid and Surface Chemistry, Protein structure, Protein folding, Carrier Proteins, Protein secondary structure, Protein Binding, Entropy (order and disorder)
Abstract

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.

Published
2004
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2. Side-chain interactions form late and cooperatively in the binding reaction between disordered peptides and PDZ domains

Author

Åke Engström, Celestine N. Chi, Andreas Karlsson, Anders Bach, Greta Hultqvist, Kristian Strømgaard, Per Jemth, Jakob Dogan, Linda Celeste Montemiglio, S. Raza Haq, Patrik Lundström, and Stefano Gianni

Subjects
Models, Molecular, PDZ domain, Molecular binding, PDZ Domains, Model system, Plasma protein binding, Intrinsically disordered proteins, Ligands, Biochemistry, Catalysis, Colloid and Surface Chemistry, Models, Mammalian cell, Side chain, Linear Models, Peptides, Protein Binding, Thermodynamics, Chemistry (all), Chemistry, Molecular, General Chemistry, Kemi, Affinities, Crystallography, Chemical Sciences, Biophysics
Abstract

Intrinsically disordered proteins are very common and mediate numerous protein-protein and protein-DNA interactions. While it is clear that these interactions are instrumental for the life of the mammalian cell, there is a paucity of data regarding their molecular binding mechanisms. Here we have used short peptides as a model system for intrinsically disordered proteins. Linear free energy relationships based on rate and equilibrium constants for the binding of these peptides to ordered target proteins, PDZ domains, demonstrate that native side-chain interactions form mainly after the rate-limiting barrier for binding and in a cooperative fashion. This finding suggests that these disordered peptides first form a weak encounter complex with non-native interactions. The data do not support the recent notion that the affinities of intrinsically disordered proteins toward their targets are generally governed by their association rate constants. Instead, we observed the opposite for peptide-PDZ interactions, namely, that changes in K(d) correlate with changes in k(off).

Published
2011

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