A mutation causing reduced biological activity and stability of thyroxine-binding globulin probably as a result of abnormal glycosylation of the molecule

Molecular Endocrinology
Y MoriS Refetoff

Abstract

T4-binding globulin (TBG), a 54-kilodalton glycoprotein, is the major thyroid hormone transport protein in man. The exact nature of the mutations causing X chromosome-linked TBG deficiency, which affect about 1 in 2,500 newborn males, is unknown. Here we report the sequence of a unique variant TBG (TBG-Gary) encoding a protein with severely impaired T4 binding as well as decreased stability at 37 C, resulting in its rapid in vivo denaturation. A single nucleotide substitution in the codon for residue 96 of the mature protein replaces isoleucine with asparagine; this replacement creates an additional site for N-linked glycosylation. The anodal shift of TBG-Gary on isoelectric focusing gel electrophoresis suggests that this new site is likely glycosylated. Since glycosylated is required for TBG to assume its correct tertiary structure, but is not subsequently necessary for maintenance of the biological properties or stability of the molecule, we believe that the likely presence of additional carbohydrate probably affects a higher order structure of the molecule and is thus responsible for the reduced stability and hormone binding activity of TBG-Gary (TBGASN-96).

Citations

Sep 2, 2006·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Deborah MannavolaPaolo Beck-Peccoz
Aug 1, 1992·The Journal of Steroid Biochemistry and Molecular Biology·C L SmithG L Hammond
Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·R B ParadA E Davis
Oct 16, 2003·Thyroid : Official Journal of the American Thyroid Association·Meyer Knobel, Geraldo Medeiros-Neto
Aug 10, 2000·Protein Science : a Publication of the Protein Society·P R ElliottD A Lomas
Apr 1, 1990·Journal of Endocrinological Investigation·M R WaltzS Refetoff
Nov 3, 2015·Best Practice & Research. Clinical Endocrinology & Metabolism·Theodora PappaSamuel Refetoff
Mar 1, 1992·Trends in Endocrinology and Metabolism : TEM·O E JanssenS Refetoff
Apr 25, 2015·Thyroid Research·Katarzyna Lacka, Adam Maciejewski
Jun 23, 2016·Molecular Genetics and Metabolism Reports·Fahimeh SoheilipourBabak Behnam
Jul 28, 2016·Annals of Pediatric Endocrinology & Metabolism·Hye Young Jin
Jul 29, 2019·Journal of Endocrinological Investigation·M S Mimoto, S Refetoff
May 1, 1993·Journal of Endocrinological Investigation·L Bartalena
Nov 24, 1995·The Journal of Biological Chemistry·O E JanssenP C Scriba

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