A. Zen, C. Micheletti, O. Keskin and R. Nussinov
Comparing interfacial dynamics in protein-protein complexes: an elastic network approach
BMC Struct. Biol., 2010 10:26 doi:10.11\
86/1472-6807-10-26
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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.