Human COA3 Is an Oligomeric Highly Flexible Protein in Solution
Por:
Neira, J, Martinez-Rodrituez, S, Hernandez-Cifre, J, Camara-Artigas, A, Clemente, P, Peralta, S, Fernandez-Moreno, M, Garesse, R, de la Torre, J and Rizzuti, B
Publicada:
15 nov 2016
Categoría:
Biochemistry
Resumen:
The assembly of the protein complex of cytochrome c oxidase (COX), which participates in the mitochondrial respiratory chain, requires a large number of accessory proteins (the so-called assembly factors). Human COX assembly factor 3 (hCOA3), also known as MITRAC12 or coiled-coil domain-containing protein 56 (CCDC56), interacts with the first subunit protein of COX to form its catalytic core and promotes its assemblage with the other units. Therefore, hCOA3 is involved in COX biogenesis in humans and can be exploited as a drug target in patients with mitochondrial dysfunctions. However, to be considered a molecular target, its structure and conformational stability must first be elucidated. We have embarked on the description of such features by using spectroscopic and hydrodynamic techniques, in aqueous solution and in the presence of detergents, together with computational methods. Our results show that hCOA3 is an oligomeric protein, forming aggregates of different molecular masses in aqueous solution. Moreover, on the basis of fluorescence and circular dichroism results, the protein has (i) its unique tryptophan partially shielded from solvent and (ii) a relatively high percentage of secondary structure. However, this structure is highly flexible and does not involve hydrogen bonding. Experiments in the presence of detergents suggest a slightly higher content of nonrigid helical structure. Theoretical results, based on studies of the primary structure of the protein, further support the idea that hCOA3 is a disordered protein. We suggest that the flexibility of hCOA3 is crucial for its interaction with other proteins to favor mitochondrial protein translocation and assembly of proteins involved in the respiratory chain.
Filiaciones:
:
Univ Miguel Hernandez, Inst Biol Mol & Celular, Edificio Torregaitan,Avda Ferrocarril S-N, Alicante 03202, Spain
Biocomp & Complex Syst Phys Inst, Zaragoza, Spain
Martinez-Rodrituez, S:
Univ Miguel Hernandez, Inst Biol Mol & Celular, Edificio Torregaitan,Avda Ferrocarril S-N, Alicante 03202, Spain
Univ Granada, Dept Phys Chem, Granada, Spain
Hernandez-Cifre, J:
Univ Murcia, Dept Phys Chem, Murcia, Spain
Camara-Artigas, A:
Univ Almeria, Dept Chem & Phys, Agrifood Campus Int Excellence CeiA3, Almeria, Spain
Clemente, P:
Univ Autonoma Madrid, CSIC, Dept Bioquim, Inst Invest Biomed Alberto Sols, Madrid, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Hosp 12 Octubre I 12, Inst Invest Sanitaria, Madrid, Spain
Karolinska Inst, Dept Lab Med, Stockholm, Sweden
Peralta, S:
Univ Autonoma Madrid, CSIC, Dept Bioquim, Inst Invest Biomed Alberto Sols, Madrid, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Hosp 12 Octubre I 12, Inst Invest Sanitaria, Madrid, Spain
Univ Miami, Miller Sch Med, Miami, FL 33136 USA
Fernandez-Moreno, M:
Univ Autonoma Madrid, CSIC, Dept Bioquim, Inst Invest Biomed Alberto Sols, Madrid, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Hosp 12 Octubre I 12, Inst Invest Sanitaria, Madrid, Spain
Garesse, R:
Univ Autonoma Madrid, CSIC, Dept Bioquim, Inst Invest Biomed Alberto Sols, Madrid, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Hosp 12 Octubre I 12, Inst Invest Sanitaria, Madrid, Spain
de la Torre, J:
Univ Murcia, Dept Phys Chem, Murcia, Spain
Rizzuti, B:
Univ Calabria, Licryl UOS Cosenza, CNR NANOTEC, I-87036 Arcavacata Di Rende, Italy
Univ Calabria, Dept Phys, CEMIF Cal, I-87036 Arcavacata Di Rende, Italy
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