Structure and function of corticosteroid-binding globulin: Role of carbohydrates

To study the site-specificity of human corticosteroid-binding globulin (CBG) glycosylation and the functional significance of individual carbohydrate chains in its molecule, a panel of recombinant CBG mutants containing each of the six potential glycosylation sites alone and in various combinations...

Full description

Saved in:
Bibliographic Details
Published in:Journal of steroid biochemistry and molecular biology 1995-06, Vol.53 (1), p.515-522
Main Author: Avvakumov, George V.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Analytical, structural and metabolic biochemistry
Animals
Binding and carrier proteins
Biological and medical sciences
Fundamental and applied biological sciences. Psychology
Glycosylation
Humans
Hydrocortisone - metabolism
Molecular Sequence Data
Proteins
Sequence Alignment
Sequence Homology, Amino Acid
Structure-Activity Relationship
Transcortin - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:To study the site-specificity of human corticosteroid-binding globulin (CBG) glycosylation and the functional significance of individual carbohydrate chains in its molecule, a panel of recombinant CBG mutants containing each of the six potential glycosylation sites alone and in various combinations has been expressed in Chinese hamster ovary (CHO) cells. Analyses of these mutant glycoproteins showed that three of the glycosylation sites are only partially utilized, and this may contribute to the production of glycoforms with distinct physiological functions. Processing of individual carbohydrate chains (branching and fucosylation) is site-specific and may, thus, account for the formation of structural determinants essential for the recognition of CBG by cell membranes. Glycosylation at the only phylogenetically conserved consensus site, Asn 238-Gly 239-Thr 240, is essential for the biosynthesis of CBG with steroid-binding activity. Evidence has been obtained to support the hypothesis that transient carbohydrate-polypeptide interactions between Trp 266 and the maturing carbohydrate chain at Asn 238 occur during early stages of the CBG biosynthesis which affect protein folding and formation of the steroid-binding site. Another tryptophan residue, Trp 371, has been found to be critical for CBG-steroid interactions and is likely located in the steroid-binding site.
ISSN:0960-0760
1879-1220
DOI:10.1016/0960-0760(95)00099-L