Biomaterial Database

Determinants of Ascaris hemoglobin octamer formation. 1998

D M Minning, and D E Goldberg

Howard Hughes Medical Institute, Departments of Molecular Microbiology and Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

The oxygen-avid, homooctameric hemoglobin of Ascaris (AH) has an unusual structure. Each polypeptide consists of two tandem globin folds followed by a highly charged COOH-terminal tail that contains four direct repeats of His-Lys-Glu-Glu (HKEE). Deletion analysis of the AH tail determined that at least two of the four HKEE repeats are required for efficient octamer formation. Surprisingly, the first four residues of the tail (Glu-His-His-Glu) alone were moderately effective in promoting multimerization. The hemoglobin from Pseudoterranova decipiens (PH) also consists of two globin domains followed by a shorter COOH-terminal extension containing only one HKEE repeat. Interchanging the tails of AH and PH revealed that the PH tail is moderately effective in promoting octamer formation. Dissociation analysis of wild-type and mutant AH and PH revealed that the intact octamers are stabilized by interactions between residues within the globin folds, not the tail. Mutational and biochemical studies revealed that one key interaction is contributed by isoleucine 15, which lies in the unusually long AB loop of AH. We propose that the AH tail plays no role in stabilization of the quaternary structure once formed but rather functions as an intramolecular chaperone, aiding assembly of the nascent AH octamer.

UI	MeSH Term	Description	Entries
D007532	Isoleucine	An essential branched-chain aliphatic amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels.	Alloisoleucine,Isoleucine, L-Isomer,L-Isoleucine,Isoleucine, L Isomer,L-Isomer Isoleucine
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009348	Nematoda	A phylum of unsegmented helminths with fundamental bilateral symmetry and secondary triradiate symmetry of the oral and esophageal structures. Many species are parasites.	Phasmidia,Secernentea,Sipunculida
D011487	Protein Conformation	The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).	Conformation, Protein,Conformations, Protein,Protein Conformations
D006454	Hemoglobins	The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements.	Eryhem,Ferrous Hemoglobin,Hemoglobin,Hemoglobin, Ferrous
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001483	Base Sequence	The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.	DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D001704	Biopolymers	Polymers synthesized by living organisms. They play a role in the formation of macromolecular structures and are synthesized via the covalent linkage of biological molecules, especially AMINO ACIDS; NUCLEOTIDES; and CARBOHYDRATES.	Bioplastics,Bioplastic,Biopolymer
D016296	Mutagenesis	Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.	Mutageneses