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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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Distribution of sizes of (a) the first chain of the dimers reported in Table 1, and of (b) their semi-interface region.
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Figure 1: Distribution of sizes of (a) the first chain of the dimers reported in Table 1, and of (b) their semi-interface region.

Mentions: (i) Protein length: As readily seen in Table 1, the dataset covers a wide range of lengths, from 64 [PDB:1a93, 1tmz, 2a93] to 896 amino acids for oxidoreductase [PDB:1ger]. Most of the largest complexes have type I interfaces. Five of the seven complexes which have monomers comprising more than 200 residues are of type I, one is of type II and one of type III. This property is readily perceived in Figure 1a, which provides a histogram of the sizes of the first chain in Table 1 for each complex.


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

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

Distribution of sizes of (a) the first chain of the dimers reported in Table 1, and of (b) their semi-interface region.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Distribution of sizes of (a) the first chain of the dimers reported in Table 1, and of (b) their semi-interface region.
Mentions: (i) Protein length: As readily seen in Table 1, the dataset covers a wide range of lengths, from 64 [PDB:1a93, 1tmz, 2a93] to 896 amino acids for oxidoreductase [PDB:1ger]. Most of the largest complexes have type I interfaces. Five of the seven complexes which have monomers comprising more than 200 residues are of type I, one is of type II and one of type III. This property is readily perceived in Figure 1a, which provides a histogram of the sizes of the first chain in Table 1 for each complex.

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