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.

Reflections on the evolution of the vertebrate tissue inhibitors of metalloproteinases

“…This method was conducted through the Trex (www.trex.uqam.ca) and CIPRES Gateway (www.phylo.org) websites. The overall results are consistent with previous reports (2,(25)(26)(27)(28)37) in indicating that the 4 vertebrate TIMP lines were produced by 3 successive gene duplications that occurred before the separation of the Chondrichthyes (cartilaginous fish) from the vertebrate stem ( Fig. 4).…”

“…Although invertebrate TIMPs generally have 2 domains, some-including the 2 TIMPs of the nematode, Caenorhabditis elegans, TIMPs from some bivalves, and TIMP homologs from some bacteria (2)-have a single domain that corresponds to the N-domain of vertebrate TIMPs (25). Because homologs of N-TIMP are found in some bacteria, single-domain invertebrate TIMPs might be regarded as evolutionary relics of an ancestral form.…”

Keeping It All Going—Complement Meets Metabolism

“…These membrane proteins catalyze a cationic cyclization cascade converting linear triterpenes to fused ring compounds and are thought to be evolutionary precursors to sterol cyclases, which are key enzymes in cholesterol metabolism (119). Similarly, the NTR-like domain within C3, C4, and C5 is found in proteins regulating directional axonal growth and cell migration during neural development (120, 121) and in tissue inhibitors of metalloproteinases, which are instrumental in regulating extracellular matrix turnover (122). …”

Characterization of Translationally Controlled Tumour Protein from the Sea Anemone Anemonia viridis and Transcriptome Wide Identification of Cnidarian Homologues

“…Phylogenetic and molecular evolutionary analyses were conducted using a Maximum Likelihood (ML) method, implemented in MEGA version 7.0 [ 39 ] in which Poisson correction, pairwise deletion and bootstrapping (1000 replicates) were considered as parameters, to reconstruct the evolutionary diversification and the molecular evolution of TCTP proteins family in cnidarians and different Eumetazoan groups. Moreover, the 3D structures of TCTP proteins were reconstructed exploiting the advances in homologues detection [ 23 , 27 , 40 ]. Thus homology modelling via the Protein Homology/analogY Recognition Engine 2.0 (Phyre 2) software [ 41 ] using the intensive modelling mode was carried out.…”

“…Combined analyses of morphological characters and molecular data are consistent with the idea that the Anthozoans are basal within the cnidarian phylum and they best represent the primitive cnidarians [ 19 , 20 ]. Despite the occurrence of a single body axis and a diploblastic organisation, genomic and transcriptional analyses revealed unexpected ancestral complexity [ 21 , 22 , 23 ]. Extant cnidarians represent the first organisms from organized cells into tissues [ 24 ] and as sister group of the Bilateria they are of great interest for the identification of mechanisms leading to bilaterian traits [ 25 , 26 , 27 ].…”