NMR backbone dynamics studies of human PED/PEA-15 outline protein functional sites(720 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
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MacIejewski, M.W., Liu, D., Prasad, R., Wilson, S.H., Mullen, G.P., Backbone dynamics and refined solution structure of the N-terminal domain of DNA polymerase beta. Correlation with DNA binding and dRP lyase activity (2000) J Mol Biol, 296, pp. 229-253
Lee, L.K., Rance, M., Chazin, W.J., Palmer III, A.G., Rotational diffusion anisotropy of proteins from simultaneous analysis of 15N and 13C alpha nuclear spin relaxation (1997) J Biomol NMR, 9, pp. 287-298
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Farrow, N.A., Zhang, O., Forman-Kay, J.D., Kay, L.E., Comparison of the backbone dynamics of a folded and an unfolded SH3 domain existing in equilibrium in aqueous buffer (1995) Biochemistry, 34, pp. 868-878
Viles, J.H., Donne, D., Kroon, G., Prusiner, S.B., Cohen, F.E., Dyson, H.J., Wright, P.E., Local structural plasticity of the prion protein. Analysis of NMR relaxation dynamics (2001) Biochemistry, 40 (9), pp. 2743-2753. , DOI 10.1021/bi002898a
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Ferreon, J.C., Hilser, V.J., Ligand-induced changes in dynamics in the RT loop of the C-terminal SH3 domain of Sem-5 indicate cooperative conformational coupling (2003) Protein Sci, 12, pp. 982-996
Carrington, P.E., Sandu, C., Wei, Y., Hill, J.M., Morisawa, G., Huang, T., Gavathiotis, E., Werner, M.H., The structure of FADD and its mode of interaction with procaspase-8 (2006) Molecular Cell, 22 (5), pp. 599-610. , DOI 10.1016/j.molcel.2006.04.018, PII S1097276506002668
Yang, J.K., Wang, L., Zheng, L., Wan, F., Ahmed, M., Lenardo, M.J., Wu, H., Crystal structure of MC159 reveals molecular mechanism of DISC assembly and FLIP inhibition (2005) Molecular Cell, 20 (6), pp. 939-949. , DOI 10.1016/j.molcel.2005.10.023, PII S1097276505017181
Li, F.-Y., Jeffrey, P.D., Yu, J.W., Shi, Y., Crystal structure of a viral FLIP: Insights into FLIP-mediated inhibition of death receptor signaling (2006) Journal of Biological Chemistry, 281 (5), pp. 2960-2968. , http://www.jbc.org/cgi/reprint/281/5/2960.pdf, DOI 10.1074/jbc.M511074200
Shisler, J.L., Moss, B., Molluscum contagiosum virus inhibitors of apoptosis: The MC159 v-FLIP protein blocks Fas-induced activation of procaspases and degradation of the related MC160 protein (2001) Virology, 282 (1), pp. 14-25. , DOI 10.1006/viro.2001.0834
Palmer, A.G., Rance, M., Wright, P.E., Intramolecular motions of a zinc finger DNA-binding domain from Xfin characterized by proton-detected natural abundance carbon-13 heteronuclear NMR spectroscopy (1991) J Am Chem Soc, 113, pp. 4371-4380
Mandel, A.M., Akke, M., Palmer III, A.G., Backbone dynamics of Escherichia coli ribonuclease HI: Correlations with structure and function in an active enzyme (1995) J Mol Biol, 246, pp. 144-163
D'Auvergne, E.J., Gooley, P.R., The use of model selection in the model-free analysis of protein dynamics (2003) Journal of Biomolecular NMR, 25 (1), pp. 25-39. , DOI 10.1023/A:1021902006114
Farrow, N.A., Muhandiram, R., Singer, A.U., Pascal, S.M., Kay, C.M., Gish, G., Shoelson, S.E., Kay, L.E., Backbone dynamics of a free and a phosphopeptide-complexed src homology 2 domain studied by 15N NMR relaxation (1994) Biochemistry, 33 (19), pp. 5984-6003. , DOI 10.1021/bi00185a040
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