Dendrimers as Competitors of Protein-Protein Interactions of the Intrinsically Disordered Nuclear Chromatin Protein NUPR1
Por:
Neira, J, Correa, J, Rizzuti, B, Santofimia-Castano, P, Abian, O, Velazquez-Campoy, A, Fernandez-Megia, E and Iovanna, J
Publicada:
1 jul 2019
Resumen:
NUPR1 is a protumoral multifunctional intrinsically disordered protein, which is activated during the acute phases of pancreatitis, interacting with several biomolecules through residues around Ala33 and Thr68. Because of the large size of this hot-spot, designed small molecules could be insufficient to modulate all NUPR1 functions. In this work we studied NUPR1 interactions with dendrimers by using biophysical techniques and in silico methods. Our results, obtained with different functionalized dendrimers (anionic, cationic and neutral) and several of their generations, indicate that NUPR1 was bound to the dendrimers. Functionalities at the dendrimer periphery modulated the affinity for NUPR1, and for any dendrimer, the affinity increased with generation. The affinities of most of the dendrimers were in the range 4-40 x 10(3) M-1, and those of the [Gn]-PhCO2Na dendrimers were similar to those of NUPR1 for its natural partners (0.1-1 X 10(6) M-1). In all dendrimers, the residues of NUPR1 first affected upon binding were located around Ala33, indicating that NUPR1 employs the same hot-spot to recognize any natural or synthetic molecule.
Filiaciones:
:
Univ Miguel Hernandez, Inst Biol Mol & Celular, Alicante 03202, Spain
Univ Zaragoza, Joint Units IQFR CSIC BIFI, Inst Biocomputac & Fis Sistemas Complejos BIFI, Zaragoza 50018, Spain
Univ Zaragoza, GBsC CSIC BIFI, Zaragoza 50018, Spain
Correa, J:
Univ Santiago de Compostela, Ctr Singular Invest Quim Biolox & Mat Mol CIQUS, Jenaro de la Fuente S-N, La Coruna 15782, Spain
Univ Santiago de Compostela, Dept Quim Organ, Jenaro de la Fuente S-N, La Coruna 15782, Spain
Rizzuti, B:
Univ Calabria, Licryl UOS Consenza, CNR NANOTEC, Via P Bucci,Cubo 31 C, I-87036 Cosenza, Italy
Univ Calabria, CEMIF Cal, Dept Phys, Via P Bucci,Cubo 31 C, I-87036 Cosenza, Italy
Santofimia-Castano, P:
Aix Marseille Univ, CNRS, UMR 7258, CRCM,INSERM,U1068, Parc Sci & Technol Luminy,163 Ave Luminy, F-13288 Marseille, France
Inst Paoli Calmettes, Parc Sci & Technol Luminy,163 Ave Luminy, F-13288 Marseille, France
Abian, O:
Univ Zaragoza, Joint Units IQFR CSIC BIFI, Inst Biocomputac & Fis Sistemas Complejos BIFI, Zaragoza 50018, Spain
Univ Zaragoza, GBsC CSIC BIFI, Zaragoza 50018, Spain
Aragon Inst Hlth Res IIS Aragon, Zaragoza 50009, Spain
Ctr Invest Biomed Red Area Temat Enfermedades Hep, Madrid 28029, Spain
Univ Zaragoza, Dept Bioquim & Biol Mol & Celular, Zaragoza 50018, Spain
IACS, Zaragoza 50009, Spain
Velazquez-Campoy, A:
Univ Zaragoza, Joint Units IQFR CSIC BIFI, Inst Biocomputac & Fis Sistemas Complejos BIFI, Zaragoza 50018, Spain
Univ Zaragoza, GBsC CSIC BIFI, Zaragoza 50018, Spain
Aragon Inst Hlth Res IIS Aragon, Zaragoza 50009, Spain
Ctr Invest Biomed Red Area Temat Enfermedades Hep, Madrid 28029, Spain
Univ Zaragoza, Dept Bioquim & Biol Mol & Celular, Zaragoza 50018, Spain
Govt Aragon, Fdn ARAID, Zaragoza 50018, Spain
Fernandez-Megia, E:
Univ Santiago de Compostela, Ctr Singular Invest Quim Biolox & Mat Mol CIQUS, Jenaro de la Fuente S-N, La Coruna 15782, Spain
Univ Santiago de Compostela, Dept Quim Organ, Jenaro de la Fuente S-N, La Coruna 15782, Spain
Iovanna, J:
Aix Marseille Univ, CNRS, UMR 7258, CRCM,INSERM,U1068, Parc Sci & Technol Luminy,163 Ave Luminy, F-13288 Marseille, France
Inst Paoli Calmettes, Parc Sci & Technol Luminy,163 Ave Luminy, F-13288 Marseille, France
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