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Comparing interfacial dynamics in protein-protein complexes: an elastic network approach.

Zen A, Micheletti C, Keskin O, Nussinov R - BMC Struct. Biol. (2010)

Bottom Line: The change in interfacial mobility upon removing "in silico" the partner monomer (unbound form) was next found to be correlated with the interface type, size and obligate nature of the complex.In particular, going from the unbound to the bound forms, the interfacial mobility is noticeably reduced for dimers with type I interfaces, while it is largely unchanged for type II ones.The results suggest that these structurally- and biologically-different types of interfaces are stabilized by different balancing mechanisms between enthalpy and conformational entropy.

View Article: PubMed Central - HTML - PubMed

Affiliation: SISSA, Democritos CNR-IOM and Italian Institute of Technology, Via Bonomea 265, 34136 Trieste, Italy.

ABSTRACT

Background: The transient, or permanent, association of proteins to form organized complexes is one of the most common mechanisms of regulation of biological processes. Systematic physico-chemical studies of the binding interfaces have previously shown that a key mechanism for the formation/stabilization of dimers is the steric and chemical complementarity of the two semi-interfaces. The role of the fluctuation dynamics at the interface of the interacting subunits, although expectedly important, proved more elusive to characterize. The aim of the present computational study is to gain insight into salient dynamics-based aspects of protein-protein interfaces.

Results: The interface dynamics was characterized by means of an elastic network model for 22 representative dimers covering three main interface types. The three groups gather dimers sharing the same interface but with good (type I) or poor (type II) similarity of the overall fold, or dimers sharing only one of the semi-interfaces (type III). The set comprises obligate dimers, which are complexes for which no structural representative of the free form(s) is available. Considerations were accordingly limited to bound and unbound forms of the monomeric subunits of the dimers. We proceeded by first computing the mobility of amino acids at the interface of the bound forms and compare it with the mobility of (i) other surface amino acids (ii) interface amino acids in the unbound forms. In both cases different dynamic patterns were observed across interface types and depending on whether the interface belongs to an obligate or non-obligate complex.

Conclusions: The comparative investigation indicated that the mobility of amino acids at the dimeric interface is generally lower than for other amino acids at the protein surface. The change in interfacial mobility upon removing "in silico" the partner monomer (unbound form) was next found to be correlated with the interface type, size and obligate nature of the complex. In particular, going from the unbound to the bound forms, the interfacial mobility is noticeably reduced for dimers with type I interfaces, while it is largely unchanged for type II ones. The results suggest that these structurally- and biologically-different types of interfaces are stabilized by different balancing mechanisms between enthalpy and conformational entropy.

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Scatter plot of the mobility of amino acid at semi-interfaces of bound and unbound monomers. The symbols and colors of the data points reflect the secondary structure type.
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Figure 5: Scatter plot of the mobility of amino acid at semi-interfaces of bound and unbound monomers. The symbols and colors of the data points reflect the secondary structure type.

Mentions: Finally, we consider the secondary-structure content of the semi-interfaces and its correlation with the three types of scenarios. To address this point, the data of Figure 4 have been reproduced in Figure 5 using a color scheme depending on the secondary structure to which each amino acid belongs. The plot for type I, see panel (a), indicates that the highest "unrestricted" fluctuation is for interface residues belonging to loops and beta strands. These amino acids experience the largest variation in the fluctuation due to the influence of the partner monomer. In the plot for type II, see panel (b), the interface residues are mainly in alpha-helices (excluding some beta strands that came from [PDB:1a15]). In the plot for type III, see panel (c), most of the more fluctuating residues are alpha-helices.


Comparing interfacial dynamics in protein-protein complexes: an elastic network approach.

Zen A, Micheletti C, Keskin O, Nussinov R - BMC Struct. Biol. (2010)

Scatter plot of the mobility of amino acid at semi-interfaces of bound and unbound monomers. The symbols and colors of the data points reflect the secondary structure type.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2927602&req=5

Figure 5: Scatter plot of the mobility of amino acid at semi-interfaces of bound and unbound monomers. The symbols and colors of the data points reflect the secondary structure type.
Mentions: Finally, we consider the secondary-structure content of the semi-interfaces and its correlation with the three types of scenarios. To address this point, the data of Figure 4 have been reproduced in Figure 5 using a color scheme depending on the secondary structure to which each amino acid belongs. The plot for type I, see panel (a), indicates that the highest "unrestricted" fluctuation is for interface residues belonging to loops and beta strands. These amino acids experience the largest variation in the fluctuation due to the influence of the partner monomer. In the plot for type II, see panel (b), the interface residues are mainly in alpha-helices (excluding some beta strands that came from [PDB:1a15]). In the plot for type III, see panel (c), most of the more fluctuating residues are alpha-helices.

Bottom Line: The change in interfacial mobility upon removing "in silico" the partner monomer (unbound form) was next found to be correlated with the interface type, size and obligate nature of the complex.In particular, going from the unbound to the bound forms, the interfacial mobility is noticeably reduced for dimers with type I interfaces, while it is largely unchanged for type II ones.The results suggest that these structurally- and biologically-different types of interfaces are stabilized by different balancing mechanisms between enthalpy and conformational entropy.

View Article: PubMed Central - HTML - PubMed

Affiliation: SISSA, Democritos CNR-IOM and Italian Institute of Technology, Via Bonomea 265, 34136 Trieste, Italy.

ABSTRACT

Background: The transient, or permanent, association of proteins to form organized complexes is one of the most common mechanisms of regulation of biological processes. Systematic physico-chemical studies of the binding interfaces have previously shown that a key mechanism for the formation/stabilization of dimers is the steric and chemical complementarity of the two semi-interfaces. The role of the fluctuation dynamics at the interface of the interacting subunits, although expectedly important, proved more elusive to characterize. The aim of the present computational study is to gain insight into salient dynamics-based aspects of protein-protein interfaces.

Results: The interface dynamics was characterized by means of an elastic network model for 22 representative dimers covering three main interface types. The three groups gather dimers sharing the same interface but with good (type I) or poor (type II) similarity of the overall fold, or dimers sharing only one of the semi-interfaces (type III). The set comprises obligate dimers, which are complexes for which no structural representative of the free form(s) is available. Considerations were accordingly limited to bound and unbound forms of the monomeric subunits of the dimers. We proceeded by first computing the mobility of amino acids at the interface of the bound forms and compare it with the mobility of (i) other surface amino acids (ii) interface amino acids in the unbound forms. In both cases different dynamic patterns were observed across interface types and depending on whether the interface belongs to an obligate or non-obligate complex.

Conclusions: The comparative investigation indicated that the mobility of amino acids at the dimeric interface is generally lower than for other amino acids at the protein surface. The change in interfacial mobility upon removing "in silico" the partner monomer (unbound form) was next found to be correlated with the interface type, size and obligate nature of the complex. In particular, going from the unbound to the bound forms, the interfacial mobility is noticeably reduced for dimers with type I interfaces, while it is largely unchanged for type II ones. The results suggest that these structurally- and biologically-different types of interfaces are stabilized by different balancing mechanisms between enthalpy and conformational entropy.

Show MeSH
Related in: MedlinePlus