title: Functional dynamics of PDZ binding domains: a normal-mode analysis.
abstract: Postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domains are relatively small (80-120 residues) protein binding modules central in the organization of receptor clusters and in the association of cellular proteins. Their main function is to bind C-terminals of selected proteins that are recognized through specific amino acids in their carboxyl end. Binding is associated with a deformation of the PDZ native structure and is responsible for dynamical changes in regions not in direct contact with the target. We investigate how this deformation is related to the harmonic dynamics of the PDZ structure and show that one low-frequency collective normal mode, characterized by the concerted movements of different secondary structures, is involved in the binding process. Our results suggest that even minimal structural changes are responsible for communication between distant regions of the protein, in agreement with recent NMR experiments. Thus, PDZ domains are a very clear example of how collective normal modes are able to characterize the relation between function and dynamics of proteins, and to provide indications on the precursors of binding/unbinding events.
authors.affiliation: Laboratoire de Biophysique Statistique, ITP, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland. paolo.delosrios@epfl.ch
authors.forename: Paolo
authors.initials: P
authors.lastname: De Los Rios
authors.forename: Fabio
authors.initials: F
authors.lastname: Cecconi
authors.forename: Anna
authors.initials: A
authors.lastname: Pretre
authors.forename: Giovanni
authors.initials: G
authors.lastname: Dietler
authors.forename: Olivier
authors.initials: O
authors.lastname: Michielin
authors.forename: Francesco
authors.initials: F
authors.lastname: Piazza
authors.forename: Brice
authors.initials: B
authors.lastname: Juanico
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D016880:Anisotropy; D001665:Binding Sites; D001703:Biophysics / Q000379:methods*; D002244:Carbon / Q000737:chemistry; D018360:Crystallography, X-Ray; D006160:Guanosine Triphosphate / Q000737:chemistry; D006358:Hot Temperature; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015233:Models, Statistical; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D012984:Software; D013696:Temperature; D013816:Thermodynamics
chemical_list: D008024:Ligands; D010455:Peptides; D002244:Carbon; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate