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Globular and disordered-the non-identical twins in protein-protein interactions.

Teilum K, Olsen JG, Kragelund BB - Front Mol Biosci (2015)

Bottom Line: The interactions between intrinsically disordered proteins (IDPs) and other proteins rely on changes in flexibility and this is seen as a strong determinant for their function.This has fostered the notion that IDP's bind with low affinity but high specificity.We find that ordered proteins and the disordered ones act as non-identical twins operating by similar principles but where the disordered proteins complexes are on average less stable by 2.5 kcal mol(-1).

View Article: PubMed Central - PubMed

Affiliation: Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen Copenhagen, Denmark.

ABSTRACT
In biology proteins from different structural classes interact across and within classes in ways that are optimized to achieve balanced functional outputs. The interactions between intrinsically disordered proteins (IDPs) and other proteins rely on changes in flexibility and this is seen as a strong determinant for their function. This has fostered the notion that IDP's bind with low affinity but high specificity. Here we have analyzed available detailed thermodynamic data for protein-protein interactions to put to the test if the thermodynamic profiles of IDP interactions differ from those of other protein-protein interactions. We find that ordered proteins and the disordered ones act as non-identical twins operating by similar principles but where the disordered proteins complexes are on average less stable by 2.5 kcal mol(-1).

No MeSH data available.


Related in: MedlinePlus

Thermodynamics of 196 protein-protein complexes. (A) Histogram of the binding free energy, ΔG°, for complexes between two ordered proteins (red) and one ordered and one disordered protein (blue). Both distributions were fit to a Gaussian distribution (solid lines). (B) Plot of ΔH° versus TΔS° for the same protein–protein complexes with the same color code as in (A). The solid lines represent the best linear fits to the data.
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Figure 2: Thermodynamics of 196 protein-protein complexes. (A) Histogram of the binding free energy, ΔG°, for complexes between two ordered proteins (red) and one ordered and one disordered protein (blue). Both distributions were fit to a Gaussian distribution (solid lines). (B) Plot of ΔH° versus TΔS° for the same protein–protein complexes with the same color code as in (A). The solid lines represent the best linear fits to the data.

Mentions: Recall the basic thermodynamic relation, ΔG0 = ΔH0 − TΔS0 in which the entropy-enthalpy compensation infers that ΔH0 and TΔS0 are highly correlated (Brady and Sharp, 1997; Williams et al., 2004; Teilum et al., 2009). Thus, ΔG0 for the complexes in the selected sets covers a narrow range from −19.8 kcal mol−1 to −4.2 kcal mol−1 (corresponding to Kd from 3 fM to 830 μM) compared to ΔH0 and TΔS0 that are found in the ranges from −66.7 to 19.9 kcal mol−1 and from −56.1 to 28.5 kcal mol−1, respectively. The analysis of the thermodynamic parameters shows that the enthalpy (ΔH°) and the entropy (ΔS°) for binding are not significantly different between the two groups of proteins (t-test, P > 0.1). However, the average entropic contribution (−TΔS°) to the binding free energy for interactions between two ordered proteins is 2.5 ± 1.6 kcal mol−1 smaller (more stabilizing) than for interactions between an ordered and a disordered protein. Within both groups there is a linear correlation between TΔS° and ΔH° (ORD-ORD: slope = 1.09 ± 0.03, r = 0.97; ORD-IDP: slope = 1.06 ± 0.02, r = 0.98), which demonstrates a similar entropy-enthalpy compensation (Figure 2A). Thus, the same underlying thermodynamic principles are true for both groups.


Globular and disordered-the non-identical twins in protein-protein interactions.

Teilum K, Olsen JG, Kragelund BB - Front Mol Biosci (2015)

Thermodynamics of 196 protein-protein complexes. (A) Histogram of the binding free energy, ΔG°, for complexes between two ordered proteins (red) and one ordered and one disordered protein (blue). Both distributions were fit to a Gaussian distribution (solid lines). (B) Plot of ΔH° versus TΔS° for the same protein–protein complexes with the same color code as in (A). The solid lines represent the best linear fits to the data.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496568&req=5

Figure 2: Thermodynamics of 196 protein-protein complexes. (A) Histogram of the binding free energy, ΔG°, for complexes between two ordered proteins (red) and one ordered and one disordered protein (blue). Both distributions were fit to a Gaussian distribution (solid lines). (B) Plot of ΔH° versus TΔS° for the same protein–protein complexes with the same color code as in (A). The solid lines represent the best linear fits to the data.
Mentions: Recall the basic thermodynamic relation, ΔG0 = ΔH0 − TΔS0 in which the entropy-enthalpy compensation infers that ΔH0 and TΔS0 are highly correlated (Brady and Sharp, 1997; Williams et al., 2004; Teilum et al., 2009). Thus, ΔG0 for the complexes in the selected sets covers a narrow range from −19.8 kcal mol−1 to −4.2 kcal mol−1 (corresponding to Kd from 3 fM to 830 μM) compared to ΔH0 and TΔS0 that are found in the ranges from −66.7 to 19.9 kcal mol−1 and from −56.1 to 28.5 kcal mol−1, respectively. The analysis of the thermodynamic parameters shows that the enthalpy (ΔH°) and the entropy (ΔS°) for binding are not significantly different between the two groups of proteins (t-test, P > 0.1). However, the average entropic contribution (−TΔS°) to the binding free energy for interactions between two ordered proteins is 2.5 ± 1.6 kcal mol−1 smaller (more stabilizing) than for interactions between an ordered and a disordered protein. Within both groups there is a linear correlation between TΔS° and ΔH° (ORD-ORD: slope = 1.09 ± 0.03, r = 0.97; ORD-IDP: slope = 1.06 ± 0.02, r = 0.98), which demonstrates a similar entropy-enthalpy compensation (Figure 2A). Thus, the same underlying thermodynamic principles are true for both groups.

Bottom Line: The interactions between intrinsically disordered proteins (IDPs) and other proteins rely on changes in flexibility and this is seen as a strong determinant for their function.This has fostered the notion that IDP's bind with low affinity but high specificity.We find that ordered proteins and the disordered ones act as non-identical twins operating by similar principles but where the disordered proteins complexes are on average less stable by 2.5 kcal mol(-1).

View Article: PubMed Central - PubMed

Affiliation: Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen Copenhagen, Denmark.

ABSTRACT
In biology proteins from different structural classes interact across and within classes in ways that are optimized to achieve balanced functional outputs. The interactions between intrinsically disordered proteins (IDPs) and other proteins rely on changes in flexibility and this is seen as a strong determinant for their function. This has fostered the notion that IDP's bind with low affinity but high specificity. Here we have analyzed available detailed thermodynamic data for protein-protein interactions to put to the test if the thermodynamic profiles of IDP interactions differ from those of other protein-protein interactions. We find that ordered proteins and the disordered ones act as non-identical twins operating by similar principles but where the disordered proteins complexes are on average less stable by 2.5 kcal mol(-1).

No MeSH data available.


Related in: MedlinePlus