title: A single amino acid substitution in an ectopic alpha subunit of a human carcinoma choriogonadotropin.
abstract: Human choriogonadotropin [hCG] has two dissimilar noncovalently associated subunits, designated alpha and beta. An ectopically secreted hCG alpha subunit that fails to associate with the beta subunit and displays an anomalously high molecular weight on molecular sieve chromatography but not on sodium dodecyl sulfate-polyacrylamide gel electrophoresis has been sequenced. A single substitution of Glu56 by Ala56 has been found in the altered subunit. No evidence for conformational differences between normal and ectopic alpha could be found using circular dichroism or intrinsic fluorescence as measures of secondary and tertiary structure, respectively. Hydrophobicity profiles as determined by the method of Kyte and Doolittle (Kyte, J., and Doolittle, R. F. (1982) J. Mol. Biol. 157, 105-132) predicted, however, that the hydrophilic segment, Thr54-Ser55-Glu56-Ser57-Thr58, becomes an extension of the preceding hydrophobic segment when Glu56 is substituted with Ala. This solitary hemoglobin S-like mutation may lead to an altered tertiary structure, self dimerization, or an alteration in glycosylation that could be responsible for the ectopic alpha subunit's failure to associate with the beta subunit.
authors.forename: R
authors.initials: R
authors.lastname: Nishimura
authors.forename: J
authors.initials: J
authors.lastname: Shin
authors.forename: I
authors.initials: I
authors.lastname: Ji
authors.forename: C R
authors.initials: CR
authors.lastname: Middaugh
authors.forename: W
authors.initials: W
authors.lastname: Kruggel
authors.forename: R V
authors.initials: RV
authors.lastname: Lewis
authors.forename: T H
authors.initials: TH
authors.lastname: Ji
mesh_terms: D000409:Alanine; D000595:Amino Acid Sequence; D006063:Chorionic Gonadotropin / Q000302:isolation & purification*; D002942:Circular Dichroism; D005260:Female; D005971:Glutamates; D018698:Glutamic Acid; D006801:Humans; D046911:Macromolecular Substances; D011247:Pregnancy; D011487:Protein Conformation; D014328:Trophoblastic Neoplasms / Q000032:analysis*
chemical_list: D006063:Chorionic Gonadotropin; D005971:Glutamates; D046911:Macromolecular Substances; D018698:Glutamic Acid; D000409:Alanine