title: A novel two-over-two alpha-helical sandwich fold is characteristic of the truncated hemoglobin family.
abstract: Small hemoproteins displaying amino acid sequences 20-40 residues shorter than (non-)vertebrate hemoglobins (Hbs) have recently been identified in several pathogenic and non-pathogenic unicellular organisms, and named 'truncated hemoglobins' (trHbs). They have been proposed to be involved not only in oxygen transport but also in other biological functions, such as protection against reactive nitrogen species, photosynthesis or to act as terminal oxidases. Crystal structures of trHbs from the ciliated protozoan Paramecium caudatum and the green unicellular alga Chlamydomonas eugametos show that the tertiary structure of both proteins is based on a 'two-over-two' alpha-helical sandwich, reflecting an unprecedented editing of the classical 'three-over-three' alpha-helical globin fold. Based on specific Gly-Gly motifs the tertiary structure accommodates the deletion of the N-terminal A-helix and replacement of the crucial heme-binding F-helix with an extended polypeptide loop. Additionally, concerted structural modifications allow burying of the heme group and define the distal site, which hosts a TyrB10, GlnE7 residue pair. A set of structural and amino acid sequence consensus rules for stabilizing the fold and the bound heme in the trHbs homology subfamily is deduced.
authors.affiliation: Department of Physics - INFM and Advanced Biotechnology Center - IST, University of Genova, Largo Rosanna Benzi 10, 16132 Genova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pesce
authors.forename: M
authors.initials: M
authors.lastname: Couture
authors.forename: S
authors.initials: S
authors.lastname: Dewilde
authors.forename: M
authors.initials: M
authors.lastname: Guertin
authors.forename: K
authors.initials: K
authors.lastname: Yamauchi
authors.forename: P
authors.initials: P
authors.lastname: Ascenzi
authors.forename: L
authors.initials: L
authors.lastname: Moens
authors.forename: M
authors.initials: M
authors.lastname: Bolognesi
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry*; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000737:chemistry*; D006418:Heme / Q000737:chemistry; D006420:Hemeproteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010788:Photosynthesis; D010940:Plant Proteins / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014714:Vertebrates / Q000378:metabolism; D014907:Whales / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D005656:Fungal Proteins; D006420:Hemeproteins; D010940:Plant Proteins; D015800:Protozoan Proteins; D006418:Heme; D010100:Oxygen