title: Human COA3 Is an Oligomeric Highly Flexible Protein in Solution.
abstract: 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.
authors: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández , Elche, Alicante, Spain.|Biocomputation and Complex Systems Physics Institute , Zaragoza, Spain.
authors: José L
authors: JL
authors: Neira
authors: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández , Elche, Alicante, Spain.
authors: Sergio
authors: S
authors: Martínez-Rodríguez
authors: Department of Physical Chemistry, University of Murcia , Murcia, Spain.
authors: José G
authors: JG
authors: Hernández-Cifre
authors: Department of Chemistry and Physics, University of Almería , Agrifood Campus of International Excellence (ceiA3), Almería, Spain.
authors: Ana
authors: A
authors: Cámara-Artigas
authors: Departamento de Bioquímica-Instituto de Investigaciones Biomédicas "Alberto Sols", Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Científicas and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) , Madrid, Spain.|Instituto de Investigación Sanitaria, Hospital 12 de Octubre (i+12) , Madrid, Spain.
authors: Paula
authors: P
authors: Clemente
authors: Departamento de Bioquímica-Instituto de Investigaciones Biomédicas "Alberto Sols", Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Científicas and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) , Madrid, Spain.|Instituto de Investigación Sanitaria, Hospital 12 de Octubre (i+12) , Madrid, Spain.
authors: Susana
authors: S
authors: Peralta
authors: Departamento de Bioquímica-Instituto de Investigaciones Biomédicas "Alberto Sols", Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Científicas and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) , Madrid, Spain.|Instituto de Investigación Sanitaria, Hospital 12 de Octubre (i+12) , Madrid, Spain.
authors: Miguel Ángel
authors: MÁ
authors: Fernández-Moreno
authors: Departamento de Bioquímica-Instituto de Investigaciones Biomédicas "Alberto Sols", Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Científicas and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) , Madrid, Spain.|Instituto de Investigación Sanitaria, Hospital 12 de Octubre (i+12) , Madrid, Spain.
authors: Rafael
authors: R
authors: Garesse
authors: Department of Physical Chemistry, University of Murcia , Murcia, Spain.
authors: José
authors: J
authors: García de la Torre
authors: CNR-NANOTEC, Licryl-UOS Cosenza and CEMIF.Cal, Department of Physics, University of Calabria , 87036 Rende, Italy.
authors: Bruno
authors: B
authors: Rizzuti
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D003198:Computer Simulation; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D064267:Intrinsically Disordered Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D066329:Protein Aggregates; D011485:Protein Binding; D000072417:Protein Domains; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012996:Solutions / Q000737:chemistry*
chemical_list: C578539:COA3 protein, human; D064267:Intrinsically Disordered Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D066329:Protein Aggregates; D021122:Protein Subunits; D012996:Solutions; D012967:Sodium Dodecyl Sulfate; D003576:Electron Transport Complex IV