title: Recognition pliability is coupled to structural heterogeneity: a calmodulin intrinsically disordered binding region complex.
abstract: Protein interactions within regulatory networks should adapt in a spatiotemporal-dependent dynamic environment, in order to process and respond to diverse and versatile cellular signals. However, the principles governing recognition pliability in protein complexes are not well understood. We have investigated a region of the intrinsically disordered protein myelin basic protein (MBP(145-165)) that interacts with calmodulin, but that also promiscuously binds other biomolecules (membranes, modifying enzymes). To characterize this interaction, we implemented an NMR spectroscopic approach that calculates, for each conformation of the complex, the maximum occurrence based on recorded pseudocontact shifts and residual dipolar couplings. We found that the MBP(145-165)-calmodulin interaction is characterized by structural heterogeneity. Quantitative comparative analysis indicated that distinct conformational landscapes of structural heterogeneity are sampled for different calmodulin-target complexes. Such structural heterogeneity in protein complexes could potentially explain the way that transient and promiscuous protein interactions are optimized and tuned in complex regulatory networks.
authors.affiliation: Magnetic Resonance Center (CERM), University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, Italy.
authors.forename: Malini
authors.initials: M
authors.lastname: Nagulapalli
authors.forename: Giacomo
authors.initials: G
authors.lastname: Parigi
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: Joerg
authors.initials: J
authors.lastname: Gsponer
authors.forename: George
authors.initials: G
authors.lastname: Deraos
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Bamm
authors.forename: George
authors.initials: G
authors.lastname: Harauz
authors.forename: John
authors.initials: J
authors.lastname: Matsoukas
authors.forename: Maurits R R
authors.initials: MR
authors.lastname: de Planque
authors.forename: Ioannis P
authors.initials: IP
authors.lastname: Gerothanassis
authors.forename: M Madan
authors.initials: MM
authors.lastname: Babu
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchinat
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Tzakos
mesh_terms: D001665:Binding Sites / Q000235:genetics; D002147:Calmodulin / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism; D004676:Myelin Basic Protein / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D002147:Calmodulin; D046912:Multiprotein Complexes; D004676:Myelin Basic Protein