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.
Farina
Biancamaria
B
Istituto di Biostrutture e Bioimmagini, CNR, Napoli, Italy.
Pirone
Luciano
L
Russo
Luigi
L
Viparelli
Francesca
F
Doti
Nunzianna
N
Pedone
Carlo
C
Pedone
Emilia M
EM
Fattorusso
Roberto
R
D051017:Apoptosis Regulatory Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D056004:Molecular Dynamics Simulation; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding
D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; C092039:PEA15 protein, human; D010750:Phosphoproteins