Structural Zn(II) implies a switch from fully cooperative to partly downhill folding in highly homologous proteins
| Autor: | Danilo Milardi, Maddalena Palmieri, Sabrina Esposito, Annarita Del Gatto, Fortuna Netti, Roberto Fattorusso, Paolo V. Pedone, Luigi Russo, Laura Zaccaro, Carla Isernia, Gaetano Malgieri, Ilaria Baglivo, Ivan de Paola |
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| Přispěvatelé: | M, Palmieri, G, Malgieri, L, Russo, I, Baglivo, F, Netti, S, Esposito, A, Del Gatto, L, Zaccaro, L, Rizzarelli, PV, Pedone, C, Isernia, D, Milardi, R, Fattorusso, Palmieri, M., Malgieri, Gaetano, Russo, L., Baglivo, I., Netti, F., Esposito, Sabrina, Del Gatto, A., Zaccaro, L., Rizzarelli, E., Pedone, Paolo Vincenzo, Isernia, Carla, Miliardi, D., Fattorusso, Roberto, Palmieri, M, Russo, Luigi, Baglivo, I, Netti, F, Del Gatto, A, de Paola, I, Zaccaro, L, Milardi, D |
| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular Circular dichroism Protein Folding Magnetic Resonance Spectroscopy Phi value analysis Calorimetry Biochemistry Catalysis Cofactor Colloid and Surface Chemistry THERMODYNAMIC ANALYSIS Zinc finger METAL-BINDING biology Chemistry Circular Dichroism Proteins General Chemistry Protein superfamily DNA-BINDING DOMAIN Zinc BARRIER HEIGHTS Chaperone (protein) biology.protein Biophysics Protein folding Downhill folding CYS(2)HIS(2) ZINC-FINGER |
| Zdroj: | Journal of the American Chemical Society 135 (2013): 5220–5228. doi:10.1021/ja4009562 info:cnr-pdr/source/autori:Palmieri, M ; Malgieri, G ; Russo, L ; Baglivo, I ; Esposito, S ; Netti, F ; Del Gatto, A ; de Paola, I ; Zaccaro, L ; Pedone, PV ; Isernia, C ; Milardi, D ; Fattorusso, R ./titolo:Structural Zn(II) Implies a Switch from Fully Cooperative to Partly Downhill Folding in Highly Homologous Proteins/doi:10.1021%2Fja4009562/rivista:Journal of the American Chemical Society (Print)/anno:2013/pagina_da:5220/pagina_a:5228/intervallo_pagine:5220–5228/volume:135 |
| ISSN: | 1520-5126 |
| DOI: | 10.1021/ja4009562 |
| Popis: | In the funneled landscape, proteins fold to their native states through a stochastic process in which the free energy decreases spontaneously and unfolded, transition, native, and possible intermediate states correspond to local minima or saddle points. Atomic description of the folding pathway appears therefore to be essential for a deep comprehension of the folding mechanism. In metallo-proteins, characterization of the folding pathways becomes even more complex, and therefore, despite their fundamental role in critical biological processes, little is known about their folding and assembly. The study of the mechanisms through which a cofactor influences the protein folding/unfolding reaction has been the rationale of the present study aimed at contributing to the search for cofactors' general roles in protein folding reactions. In particular, we have investigated the folding pathway of two homologous proteins, Ros87, which contains a prokaryotic zinc finger domain, and Ml4 52-151, lacking the zinc ion. Using a combination of CD, DSC and NMR techniques, we determined the thermodynamics and the structural features, at an atomic level, of the thermal unfolding of Ros87 and compared them to the behavior of Ml452-151. Our results, also corroborated by NMR 1H/2H exchange measurements, show that the presence of the structural Zn(II) in Ros87 implies a switch from the Ml452-151 fully cooperative to a two-step unfolding process in which the intermediate converts to the native state through a downhill barrierless transition. This observation, which has never been reported for any metal ion so far, may have a significant role in the understanding of the protein misfolding associated with the presence of metal ions, as observed in neurodegenerative diseases. © 2013 American Chemical Society. |
| Databáze: | OpenAIRE |
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