Recognition pliability is coupled to structural heterogeneity: a calmodulin intrinsically disordered binding region complex

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Nagulapalli, M.
Parigi, G.
Yuan, J.
Gsponer, J.
Deraos, G.
Bamm, V. V.
Harauz, G.
Matsoukas, J.
de Planque, M. R.
Gerothanassis, I. P.

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Elsevier

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peer reviewed

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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.

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Binding Sites/genetics, Calmodulin/*chemistry/metabolism, *Models, Molecular, Multiprotein Complexes/*chemistry/metabolism, Myelin Basic Protein/*chemistry/metabolism, Nuclear Magnetic Resonance, Biomolecular, Protein Binding, *Protein Conformation

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http://www.ncbi.nlm.nih.gov/pubmed/22405011
http://ac.els-cdn.com/S0969212612000524/1-s2.0-S0969212612000524-main.pdf?_tid=a69c3db2-4075-11e3-915b-00000aab0f6b&acdnat=1383036160_64f32c7f993f4fe2da48b6c71b1debf3

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en

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Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας

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