114
Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session II
59-POS
Board 12
Are There any Structural Taboos in Protein-Protein Interactions? Insights from a
Genome-Wide Study of Interacting and Non Interacting Protein Pairs.
Juliette Martin
, Nicoletta Ceres, Guillaume Launay, Richard Lavery.
CNRS , Lyon, France.
Functional interactions take place between specific proteins in a healthy cell. Yet, the density of
a cell in macromolecules is such that proteins are constantly in contact or in close proximity with
other proteins that are not functional partners. How is the specificity of functional interactions
maintained? In particular, is the ability to interact encrypted in the protein's 3D structure? To
address this question we have performed an in silico large-scale experiment to explore the
structural repertoire of interacting and non-interacting proteins pairs, and to see whether they
differ.
We considered
yeast cerevisiae
, for which 3D structural models and protein-protein interaction
data are available, as well as four different data sets of nominally “negative interactions”.
Positive interactions, i.e. experimentally known interactions, were analyzed in parallel to serve as
positive control. For each interaction (positive or negative), we considered the 3D structures of
the proteins involved, and tried to determine whether the PDB contains a protein-protein
complex where similar structures interact. When a complex was found in the PDB, we qualified
the interaction as “supported” by the PDB.
We find that negative interactions selected on the basis of different sub-cellular localizations are
supported by PDB protein-protein complexes to the same extent as positive interactions. This
finding stresses the importance of physical sequestration to maintain interaction specificity.
Finally, we have analyzed the structural features of the resulting 3D models of binary protein
complexes and also their stability using our coarse-grain model PaLaCe. We found that the more
sophisticated PaLaCe energy evaluation was necessary to distinguish interacting and non-
interacting protein pairs. Interestingly, some nominally non-interacting pairs are nevertheless
predicted to form stable complexes.
