Linker chain L1 of earthworm hemoglobin. Structure of gene and protein: homology with low density lipoprotein receptor.
The extracellular hemoglobins (Hbs) of annelids and tube worms are giant multisubunit proteins of up to approximately 200 polypeptides and molecular masses to at least 3,900 kDa. They differ from all other Hbs in having both O2-binding chains and "linker" chains. The latter are required for assembly and structural integrity of the protein and are deficient in or lack heme. We have determined the nucleotide sequences of the cDNA and gene for linker chain L1 of the hemoglobin of Lumbricus terrestris. The cDNA-derived amino acid sequence has 225 residues and a calculated molecular mass of 25,847 Da. The chain is 21-28% identical to linker chains of the related annelid Tylorrhynchus heterochaetus and the deep-sea tube worm Lamellibrachia sp. A remarkable feature of the linker chains is a conserved 38-39-residue segment that contains a repeating pattern of cysteinyl residues: (Cys-X6)3-Cys-X5-Cys-X10-Cys. This pattern, not present in any globin sequence, corresponds exactly to the cysteine-rich repeats of the ligand binding domains of the low density lipoprotein (LDL) receptors of man and Xenopus laevis. Furthermore, the cysteine-rich segment of linker chain L1 has the sequence Asp-Gly-Ser-Asp-Glu which is characteristic of LDL receptor repeats. Similar cysteine-rich sequences also occur in two other mammalian proteins, complement C9 and renal glycoprotein GP330. The results support the conclusion that the cysteine-rich motif of the LDL receptor and annelid Hbs is a multipurpose protein-binding unit of ancient origin which has been incorporated into diverse unrelated proteins, presumably by the process of exon shuffling.
Department of Zoology, University of Texas, Austin 78712.
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics*; D004247:DNA; D006454:Hemoglobins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009835:Oligochaeta; D011973:Receptors, LDL / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
D001798:Blood Proteins; D006454:Hemoglobins; D011973:Receptors, LDL; C081784:hemoglobin linker chain L1 protein, Lumbricus terrestris; D004247:DNA