title: Maintenance of a Protein Structure in the Dynamic Evolution of TIMPs over 600 Million Years.
abstract: Deciphering the events leading to protein evolution represents a challenge, especially for protein families showing complex evolutionary history. Among them, TIMPs represent an ancient eukaryotic protein family widely distributed in the animal kingdom. They are known to control the turnover of the extracellular matrix and are considered to arise early during metazoan evolution, arguably tuning essential features of tissue and epithelial organization. To probe the structure and molecular evolution of TIMPs within metazoans, we report the mining and structural characterization of a large data set of TIMPs over approximately 600 Myr. The TIMPs repertoire was explored starting from the Cnidaria phylum, coeval with the origins of connective tissue, to great apes and humans. Despite dramatic sequence differences compared with highest metazoans, the ancestral proteins displayed the canonical TIMP fold. Only small structural changes, represented by an α-helix located in the N-domain, have occurred over the evolution. Both the occurrence of such secondary structure elements and the relative solvent accessibility of the corresponding residues in the three-dimensional structures raises the possibility that these sites represent unconserved element prone to accept variations.
authors.affiliation: Laboratory of Molecular Ecology and Biotechnology, National Research Council-Institute for Marine and Coastal Environment (IAMC-CNR) Detached Unit of Capo Granitola, Torretta Granitola, Trapani, Sicily, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Nicosia
authors.affiliation: Institute for Environmental Protection and Research-ISPRA, Palermo, Sicily, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Maggio
authors.affiliation: Dipartimento Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, University of Palermo, Sicily, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Costa
authors.affiliation: Laboratory of Molecular Ecology and Biotechnology, National Research Council-Institute for Marine and Coastal Environment (IAMC-CNR) Detached Unit of Capo Granitola, Torretta Granitola, Trapani, Sicily, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Salamone
authors.affiliation: Laboratory of Molecular Ecology and Biotechnology, National Research Council-Institute for Marine and Coastal Environment (IAMC-CNR) Detached Unit of Capo Granitola, Torretta Granitola, Trapani, Sicily, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tagliavia
authors.affiliation: Laboratory of Molecular Ecology and Biotechnology, National Research Council-Institute for Marine and Coastal Environment (IAMC-CNR) Detached Unit of Capo Granitola, Torretta Granitola, Trapani, Sicily, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Mazzola
authors.affiliation: Dipartimento Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, University of Palermo, Sicily, Italy fabrizio.gianguzza@unipa.it angela.cuttitta@iamc.cnr.it.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gianguzza
authors.affiliation: Laboratory of Molecular Ecology and Biotechnology, National Research Council-Institute for Marine and Coastal Environment (IAMC-CNR) Detached Unit of Capo Granitola, Torretta Granitola, Trapani, Sicily, Italy fabrizio.gianguzza@unipa.it angela.cuttitta@iamc.cnr.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Cuttitta
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003063:Cnidaria / Q000737:chemistry* / Q000235:genetics*; D017124:Conserved Sequence; D019143:Evolution, Molecular; D008958:Models, Molecular; D010802:Phylogeny; D011487:Protein Conformation; D016415:Sequence Alignment; D019714:Tissue Inhibitor of Metalloproteinases / Q000737:chemistry* / Q000235:genetics*
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases
keywords: TIMPs; cnidarians; homology modeling; transcriptome wide analysis