NMR backbone dynamics studies of human PED/PEA-15 outline protein functional sites(950 views) Farina B, Pirone L, Russo L, Viparelli F, Doti N, Pedone C, Pedone E, Fattorusso R
Keywords: Backbone Dynamics, Death Domain, Nmr Spectroscopy, Pedpea-15 Protein, Protein-Protein Interactions, Nitrogen 15, Phosphoprotein, Phosphoprotein Enriched In Diabetes Phosphoprotein Enriched In Astrocytes, Unclassified Drug, Animal Cell, Article, Human, Molecular Dynamics, Nitrogen Nuclear Magnetic Resonance, Nonhuman, Nuclear Overhauser Effect, Priority Journal, Protein Binding, Protein Domain, Protein Function, Protein Protein Interaction, Spectrometry, Steady State, Intracellular Signaling Peptides And Proteins, Magnetic Resonance Spectroscopy, Molecular Dynamics Simulation, Chemistry, Metabolism, Methods,
Affiliations: *** IBB - CNR ***
Istituto di Biostrutture e Bioimmagini, CNR, Napoli, Italy.
Dipartimento di Scienze Ambientali, Seconda Universit di Napoli, Via Vivaldi 43, 81100 Caserta, Italy
Dipartimento Delle Scienze Biologiche, Universit di Napoli Federico II, Napoli, Italy
References: Not available.
NMR backbone dynamics studies of human PED/PEA-15 outline protein functional sites
PED/PEA-15 (phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes) is a ubiquitously expressed protein and a key regulator of cell growth and glucose metabolism. PED/PEA-15 mediates both homotypic and heterotypic interactions and is constituted by an N-terminal canonical death effector domain and a C-terminal tail. In the present study, the backbone dynamics of PED/PEA-15 via (15)N R(1) and R(2) and steady-state [(1)H]-(15)N NOE measurements is reported. The dynamic parameters were analyzed using both Lipari-Szabo model-free formalism and a reduced spectral density mapping approach. The results obtained define a polar and charged surface of the death effector domain characterized by internal motions in the micro- to millisecond timescale, which is crucial for the multiple heterotypic functional protein-protein interactions in which PED/PEA-15 is involved. The present study contributes to a better understanding of the molecular basis of the PED/PEA-15 functional interactions and provides a more detailed surface for the design and development of PED/PEA-15 binders. 2010 The Authors Journal compilation 2010 FEBS.
NMR backbone dynamics studies of human PED/PEA-15 outline protein functional sites