Polar zipper sequence in the high-affinity hemoglobin of Ascaris suum: amino acid sequence and structural interpretation.
The extracellular hemoglobin of Ascaris has an extremely high oxygen affinity (P50 = 0.004 mmHg). It consists of eight identical subunits of molecular weight 40,600. Their sequence, determined by protein chemistry, shows two tandemly linked globin-like sequences and an 18-residue C-terminal extension. Two N-linked glycosylation sites contain equal ratios of mannose/glucosamine/fucose of 3:2:1. Electron micrographs suggest that the eight subunits form a polyhedron of point symmetry D4, or 42. The C-terminal extension contains a repeat of the sequence Glu-Glu-His-Lys, which would form a pattern of alternate glutamate and histidine side chains on one side and of glutamate and lysine side chains on the other side of a beta strand. We propose that this represents a polar zipper sequence and that the C-terminal extensions are joined in an eight-stranded beta barrel at the center of the molecule, with histidine and glutamate side chains inside and lysine and glutamate side chains outside the barrel compensating each other's charges. The amino acid sequence of Ascaris hemoglobin fails to explain its high oxygen affinity.
De Baere
I
I
Department of Biochemistry, University of Antwerp, Wilrijk, Belgium.
Liu
L
L
Moens
L
L
Van Beeumen
J
J
Gielens
C
C
Richelle
J
J
Trotman
C
C
Finch
J
J
Gerstein
M
M
Perutz
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001200:Ascaris / Q000235:genetics / Q000378:metabolism*; D002263:Carboxyhemoglobin / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009211:Myoglobin / Q000737:chemistry; D010108:Oxyhemoglobins / Q000378:metabolism; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid
D006454:Hemoglobins; D046911:Macromolecular Substances; D009211:Myoglobin; D010108:Oxyhemoglobins; D002263:Carboxyhemoglobin