Structural deformation upon protein-protein interaction: a structural alphabet approach.
BACKGROUND
In a number of protein-protein complexes, the 3D structures of bound and unbound partners significantly differ, supporting the induced fit hypothesis for protein-protein binding.


RESULTS
In this study, we explore the induced fit modifications on a set of 124 proteins available in both bound and unbound forms, in terms of local structure. The local structure is described thanks to a structural alphabet of 27 structural letters that allows a detailed description of the backbone. Using a control set to distinguish induced fit from experimental error and natural protein flexibility, we show that the fraction of structural letters modified upon binding is significantly greater than in the control set (36% versus 28%). This proportion is even greater in the interface regions (41%). Interface regions preferentially involve coils. Our analysis further reveals that some structural letters in coil are not favored in the interface. We show that certain structural letters in coil are particularly subject to modifications at the interface, and that the severity of structural change also varies. These information are used to derive a structural letter substitution matrix that summarizes the local structural changes observed in our data set. We also illustrate the usefulness of our approach to identify common binding motifs in unrelated proteins.


CONCLUSIONS
Our study provides qualitative information about induced fit. These results could be of help for flexible docking.
Martin
Juliette
J
Equipe de Bioinformatique Génomique et Moléculaire, INSERM UMRS726/Université Denis Diderot Paris 7, F-75005 Paris, France. juliette.martin@jouy.inra.fr
Regad
Leslie
L
Lecornet
Hélène
H
Camproux
Anne-Claude
AC
D000465:Algorithms; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D030562:Databases, Protein; D008390:Markov Chains; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary
D046912:Multiprotein Complexes