Adventitious variability? The amino acid sequences of nonvertebrate globins

Abstract

1. 1. The more than 140 amino acid sequences of non-vertebrate hemoglobins (Hbs) and myoglobins (Mbs) that are known at present, can be divided into several distinct groups: (1) single-chain globins, containing one heme-binding domain; (2) truncated, single-chain, one-domain globins; (3) chimeric, one-domain globins; (4) chimeric, two-domain globins; and (5) chimeric multi-domain globins. 2. 2. The crystal structures of eight nonvertebrate Hbs and Mbs are known, all of them monomeric, one-domain globin chains. Although these molecules represent plants, prokaryotes and several metazoan groups, and although the inter-subunit interactions in the dimeric and tetrameric molecules differ from the ones observed in vertebrate Hbs, the secondary structures of all seven one-domain globins retain the characteristic vertebrate “myoglobin fold”. No crystal structures of globins representing the other four groups have been determined. 3. 3. Furthermore, a number of the one-, two- and multi-domain globin chains participate in a broad variety of quarternary structures, ranging from homo- and heterodimers to highly complex, multisubunit aggregates with M r > 3000 kDa (S. N. Vinogradov, Comp. Biochem. Physiol. 82B, 1–15, 1985). 4. 4. (1) The single-chain, single-domain globins are comparable in size to the vertebrate globins and exhibit the widest distribution. (A) Intracellular Hbs include: (i) the monomeric and polymeric Hbs of the polychaete Glycera; (ii) the tetrameric Hb of the echiuran Urechis; (iii) the dimeric Hbs of echinoderms such as Paracaudina and Caudina; and (iv) the dimeric and tetrameric Hbs of molluscs, the bivalves Scapharca, Anadara, Barbatia and Calyptogena. (B) Extracellular Hbs include: (i) the multiple monomeric and dimeric Hbs of the larva of the insect Chironomus; (ii) the Hbs of nematodes such as Trichostrongylus and Caenorhabditis; (iii) the globin chains forming tetramers and dodecamers and comprising ∼ 2 3 of the giant (∼~ 3600 kDa), hexagonal bilayer (HBL) Hbs of annelids, e.g. the oligochaete Lumbricus and the polychaete Tylorrhynchus and of the vestimentiferan Lamellibrachia; and (iv) the globin chains comprising the ca 400 kDa Hbs of Lamellibrachia and the pogonophoran Oligobrachia. (C) Cytoplasmic Hbs include: (i) the Mbs of molluscs, the gastropods Aplysia, Bursatella, Cerithedea, Nassa and Dolabella and the chiton Liolophura; (ii) the three Hb of the symbiont-harboring bivalve Lucina; (iii) the dimeric Hb of the bacterium Vitreoscilla; and (iv) plant Hbs, including the Hbs of symbiont-containing legumes (Lgbs), the Hbs of symbiont-containing non-leguminous plants and the Hbs in the roots of symbiont-free plants. 5. 5. (2) Truncated, single-chain, single-domain globins occur in: (i) the ciliated protozoa Paramecium and Tetrahymena, comprising 116 and 121 residues, respectively; (ii) in the cyanobacterium Nostoc (118 residues) and (iii), in the nemertean Cerebratulus (109 residues). 6. 6. (3) Chimeric ≥ 40 kDa globins include: (i) the cytoplasmic Hbs in bacteria such as E. coli, Rhizobium and Alcaligenes; and (ii) in the yeasts Saccharomyces and Candida. They have an N-terminal heme-binding domain attached to unrelated proteins with diverse functions and represent, according to Riggs, a previously unrecognized evolutionary pathway for hemoglobin. In the case of Rhizobium, the relationship of the heme-binding domain to other globins is tenuous. The cytoplasmic Hb of the archeogastropod Sulculus has an internal heme-binding domain within a chain of 377 residues, whose sequence cannot be properly aligned with other globins. However, the overall primary structure has a very substantial homology to human indoleamine 2,3-dioxygenase, suggesting that Sulculus Mb is a case of convergent evolution. 7. 7. (4) Chimeric, ∼ 40 kDa globins, containing two, covalently linked heme-binding domains, comprise: (i) the extracellular, high-affinity, octameric (∼ 320 kDa) Hbs of parasitic nematodes such as Pseudoterranova and Ascaris; and (ii) the polymeric ( ca 430 kDa) intracellular Hb of the clam Barbatia. 8. 8. (5) Chimeric, linear, covalently-linked multi-domain globin sequences are represented so far by the cDNA sequence of one of the two chains comprising the extracellular Hb (∼ 250 kDa) of a crustacean, the brine shrimp Artemia, and consisting of a linear arrangement of nine heme-binding domains linked covalently by 10–20 residue sequences.