Tamm–Horsfall urinary glycoprotein. The subunit structure

Abstract

1. Subunit molecular weights of 76000-82000 were obtained for native and alkylated Tamm-Horsfall glycoprotein by gel filtration on Sephadex G-200 in the presence of sodium dodecyl sulphate. 2. A further estimate of the subunit molecular weight of 79000+/-4000 was obtained by disc gel electrophoresis in sodium dodecyl sulphate. 3. A minimum value of the chemical molecular weight of 79000+/-6000 was obtained from the number of N-terminal amino acids released by cyanogen bromide cleavage of the glycoprotein. 4. Similar values were obtained for the subunit molecular weight of Tamm-Horsfall glycoprotein from patients with cystic fibrosis. 5. On ultracentrifugation both in 1.0% sodium dodecyl sulphate and in 70% formic acid, Tamm-Horsfall glycoprotein sedimented as a single component, slightly faster than serum albumin. 6. On reduction of the disulphide bonds the same subunit molecular weight was obtained, which suggested that these bonds are intrachain.

Bence Jones proteins bind to a common peptide segment of Tamm-Horsfall glycoprotein to promote heterotypic aggregation.

“…THP is composed of 616 amino acids and has eight potential asparagine-linked glycosylation sites (9,10,22). Intramolecular disulfide bonds formed between 48 cysteine residues interspersed throughout the molecule are important in keeping a rigid structure; reducing agents do not dissociate the molecule into smaller subunits (9,22,24). The major secondary structure is a ,B-sheet with a regular zig-zag appearance (9,25).…”

Localization of a single binding site for immunoglobulin light chains on human Tamm-Horsfall glycoprotein.

“…This TammHorsfall glycoprotein (THP), 1 which has since been characterized as a 616-amino acid glycoprotein (2), is synthesized specifically by cells of the thick ascending limb of the loop of Henle (3,4). About 30% of the molecular weight of THP is carbohydrate (5). Although the physiologic significance of THP remains undefined, this protein plays an integral role in the pathologic condition known as cast nephropathy.…”

Native and/or asialo‐Tamm‐Horsfall glycoproteins Sd(a+) are important receptors for Triticum vulgaris (wheat germ) agglutinin and for three toxic lectins (abrin‐a, ricin and mistletoe toxic lectin‐I)

“…Most Tamm-Horsfall glycoproteins carry the Sd(a+) blood group active determinant, GalNAcfll 4(NeuAcc~2 --. 3)Galfll ~ 4GlcNAcfll --* 3Gal, indicating the presence of a repeating N-acetyllactosamine unit [5,6], but the rare phenotype Sd(a-) lacks the terminal GalNAc residue [6,7].THGP inhibits the mannose-dependent adhesion of Escherichia coli [1,2,8,9] and is a member of a structural glycoprotein family known to modulate cell adhesion [1]. However, little is known about the binding properties of THGP with toxic biomolecules, and/or the roles of sialic acid, N-acetyllactosamine, and chitin disaccharide (GlcNAcfll --*4GIcNAc, at the ends of the N-linked chains in the linkage region to the peptide) in the interaction of THGP with lectins.…”

“…THGP inhibits the mannose-dependent adhesion of Escherichia coli [1,2,8,9] and is a member of a structural glycoprotein family known to modulate cell adhesion [1]. However, little is known about the binding properties of THGP with toxic biomolecules, and/or the roles of sialic acid, N-acetyllactosamine, and chitin disaccharide (GlcNAcfll --*4GIcNAc, at the ends of the N-linked chains in the linkage region to the peptide) in the interaction of THGP with lectins.…”