Molecular basis of the PED/PEA15 interaction with the C-terminal fragment of phospholipase D1 revealed by NMR spectroscopy
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Molecular basis of the PED/PEA15 interaction with the C-terminal fragment of phospholipase D1 revealed by NMR spectroscopy (121 visite)

Farina B, Doti N, Pirone L, Malgieri G, Pedone E, Ruvo M, Fattorusso R

Biochim Biophys Acta (ISSN: 1570-9639, 0006-3002, 0925-4439), 2013 Sep; 1834(8): 1572-1580.

Tipo di articolo: Journal Article, Research Support, Non-U. S. Gov'T,

Impact factor: 3.191

Impact factor a 5 anni: 3.282

Parole chiave: Chemical Shift Perturbation, Death Domain, Ped Pea15 Protein, Protein-Protein Interaction, D4 Alpha Protein, Phospholipase D1, Phosphoprotein, Phosphoprotein Enriched In Astrocyte 15, Phosphoprotein Enriched In Diabetes, Protein Kinase C Alpha, Synthetic Peptide, Unclassified Drug, Human, Peptide Fragment, Signal Peptide, Allosterism, Article, Binding Site, Controlled Study, Enzyme Activity, Enzyme Linked Immunosorbent Assay, Nuclear Magnetic Resonance Spectroscopy, Priority Journal, Protein Analysis, Protein Binding, Protein Expression, Protein Protein Interaction, Chemistry, Metabolism, Protein Conformation, Enzyme-Linked Immunosorbent Assay, Intracellular Signaling Peptides And Proteins, Intracellular Signaling Peptides And Proteins Chemistry Metabolism, Peptide Fragments Chemistry Metabolism, Phospholipase D Chemistry Metabolism, Phosphoproteins Chemistry Metabolism,


PED/PEA15 is a small protein involved in many protein-protein interactions that modulates the function of a number of key cellular effectors involved in major cell functions, including apoptosis, proliferation and glucose metabolism. In particular, PED/PEA15 interacts with the phospholipase D (PLD) isoforms 1 and 2 increasing protein kinase C-alpha isoform activity and affects both insulin-stimulated glucose transport and glucose-stimulated insulin secretion. The C-terminal portion (residues 712-1074) of PLD1, named D4, is still able to interact with PED/PEA15. In this study we characterized, by means of NMR spectroscopy, the molecular interaction of PED/PEA15 with D4 alpha, a smaller region of D4, encompassing residues 712-818, shown to have the same affinity for PED/PEA15 and to induce the same effects as D4 in PED/PEA15-overexpressing cells. Chemical shift perturbation (CSP) studies allowed to define D4 alpha binding site of PED/PEA15 and to identify a smaller region likely affected by an allosteric effect. Moreover, ELISA-like experiments showed that three 20-mer overlapping synthetic peptides, covering the 762-801 region of D4 alpha, strongly inhibit PED/PEA15-D4 alpha interaction through their binding to PED/PEA15 with K(D)s in low micromolar range. Finally, molecular details of the interaction of PED/PEA15 with one of the three peptides have been revealed by CSP and saturation transfer difference (STD) analyses. (C) 2013 Elsevier B.V. All rights reserved.
*** IBB - CNR ***

Istituto di Biostrutture e Bioimmagini, CNR, Napoli, Italy

Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, via Vivaldi 43, 81100
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4 Records (2 escludendo Abstract e Conferenze).
Impact factor totale: 12.22 (7.332 escludendo Abstract e Conferenze).
Impact factor a 5 anni totale: 12.973 (7.489 escludendo Abstract e Conferenze).

Interrogazione bibliografica effettuata: (([btitle] "Chemical Shift Perturbation" OR [btitle] "Death Domain" OR [btitle] "Ped Pea15 Protein" OR [btitle] "Protein-Protein Interaction" OR [btitle] "D4 Alpha Protein") AND NOT [id] = 52208)

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