Strategies for construction of luteinizing hormone beta subunit analogs with carboxyl terminal extensions in non-primate, non-equid mammalian species.
Chorionic gonadotropins (CG) are unique because they have a carboxyl terminal peptide (CTP) extension on their beta subunits that prolongs circulatory survival. CGbeta genes from the human being and horse have evolved from ancestral luteinizing hormone (LH) beta genes by different pathways that involve deletions that change the reading frames and yield a CTP. Here we further review our previous analysis, aimed at determining whether LHbeta genes in non-primate, non-equid species inherently possess DNA sequences that encode CTP-like domains. In multiple mammalian species, simple frame-shift mutations using either the human or equine CGbeta gene as a model can be used to construct LHbeta analogs with putative CTP domains. Furthermore, DNA sequences from mammalian LHbeta genes can be aligned to maximize similarity with CGbeta genes in order to devise more refined strategies for construction of CTP-bearing LHbeta analogs as exemplified in the bovine case. Thus, mammalian LHbeta genes have DNA sequences that can be potentially expressed in order to construct CTP-bearing glycoprotein hormone analogs.
Ben-Menahem
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Department of Clinical Pharmacology, Ben-Gurion University, Faculty of Health Sciences, P.O.B. 653, Beer-Sheva 84105, Israel. dbm@bgu.ac.il
Grotjan
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HE
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D016368:Frameshift Mutation / Q000235:genetics; D006736:Horses; D006801:Humans; D007986:Luteinizing Hormone / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000235:genetics; D008322:Mammals / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D026723:Polyadenylation; D011323:Primates; D017434:Protein Structure, Tertiary; D012418:Ruminants; D017385:Sequence Homology
D018997:Chorionic Gonadotropin, beta Subunit, Human; D010455:Peptides; D007986:Luteinizing Hormone