help button home button Endocrine Society Molecular Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mori, Y.
Right arrow Articles by Refetoff, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mori, Y.
Right arrow Articles by Refetoff, S.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*Protein
*UniGene

Molecular Endocrinology, Vol 3, 575-579, Copyright © 1989 by Endocrine Society


ARTICLES

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

Y Mori, S Seino, K Takeda, IL Flink, Y Murata, GI Bell and S Refetoff
Department of Medicine, University of Chicago, Illinois 60637.

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).


This article has been cited by other articles:


Home page
J. Clin. Endocrinol. Metab.Home page
O. E. Janssen, S. T. Astner, H. Grasberger, S. K. Gunn, and S. Refetoff
Identification of Thyroxine-Binding Globulin-San Diego in a Family from Houston and Its Characterization by in Vitro Expression Using Xenopus Oocytes
J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 368 - 372.
[Abstract] [Full Text]


Home page
J. Biol. Chem.Home page
O. E. Janssen, B. Chen, C. Büttner, S. Refetoff, and P. C. Scriba
Molecular and Structural Characterization of the Heat-resistant Thyroxine-binding Globulin-Chicago
J. Biol. Chem., November 24, 1995; 270(47): 28234 - 28238.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
R. Webel, I. Menon, J. E. O'Tousa, and N. J. Colley
Role of Asparagine-linked Oligosaccharides in Rhodopsin Maturation and Association with Its Molecular Chaperone, NinaA
J. Biol. Chem., August 4, 2000; 275(32): 24752 - 24759.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1989 by The Endocrine Society