Bioinformatics Seminar
Serge Vinogradov
Wayne State University
The Superfamily of Globins: Differential Evolution of the three Globin Families
Abstract: Vertebrate hemoglobin and myoglobin were the first proteins to have their structures and sequences determined about 50 years ago. In the subsequent pregenomic period, numerous related proteins came to light in plants, invertebrates, microbial eukaryotes and bacteria, that shared the highly conserved secondary structure consisting of eight $\alpha$-helices A-H. The myoglobin fold is described as a 3-on-3 $\alpha$-helical sandwich forming a hydrophobic cavity, within which the axial positions of the bound heme group are coordinated to the side-chain groups of residues within the E and F helices. It is underpinned by a consistent set of over 30 conserved amino acid residues, and is preserved even in cases of <20% identity. Some 15 years ago, a truncated 2-on-2 $\alpha$-helical fold with a shortened or missing helix A and a loop substituting for most of helix E, was observed in algal, ciliate and some plant and bacterial globins. The list of known globins was greatly expanded by the rapid accretion of genomic information over the last 15 years, demonstrating their existence in all three domains of life, ranging from close to 100% in multicellular eukaryote genomes, to about 60% bacterial and 10% of archaeal genomes. In bacteria, all globins occur in three families: the F (flavohemoglobin) and S (sensor) families that exhibit the canonical 3/3 $\alpha$-helical fold, and the T (truncated 3/3 fold) globins characterized by the abbreviated 2/2 $\alpha$-helical fold. Chimeric and single-domain globins are found in all three globin families. Vertebrate globins now include in addition to the familiar $\alpha$- and $\beta$-globins and myoglobins, the equally ubiquitous neuroglobins and cytoglobins, and several additional globin lineages with a more limited distribution, such as GlbY, GlbX and GbE. Very recently, we have found a new metazoan globin lineage comprising large, ca. 1600 residues, chimeric proteins with an N-terminal cysteine protease domain and a central globin domain, named androglobins, because of their specific expression in testis tissue (Hoogewijs et al., 2011). All metazoan globins, including symbiotic and nonsymbiotic plant globins and many globins found in microbial eukaryotes have the 3/3 $\alpha$-helical fold and have sequences that homologous to the F family globins. T family group 1 and 2 globins occur in microbial eukaryotes (ciliates, stramenopiles, oomycets, opisthokonts, etc.) and in plants. Fungi are unique in having F and S family globins. We have proposed that eukaryote globins evolved from the respective bacterial lineage via horizontal gene transfer resulting from one or both of the accepted endosymbiotic events responsible for the origin of mitochondria and chloroplastids, involving an $\alpha$-proteobacterium and a cyanobacterium, respectively (Vinogradov et al., 2007). Within this framework, it appears evident that the F family globins that had one or more enzymatic functions in the early bacteria, evolved in multicellular eukaryotes to have new properties, including reversible binding of important diatomic ligands, namely oxygen, nitric oxide and sulfide, that permitted the development of transport and storage functions (Vinogradov and Moens, 2008). Furthermore, it is also clear that the evolutionary success of the F family has far outstripped that of the other two globin families.
Currently, we are engaged in unraveling the evolutionary history of globins in metazoans. The first step has been the identification of at least four distinct globin paralogs in the deuterostome common ancestor (Hoffmann et al., 2012).
Friday February 10, 2012 at 4:00 PM in SEO 1207