Bence Jones proteins bind to a common peptide segment of Tamm-Horsfall glycoprotein to promote heterotypic aggregation.
Bence Jones proteins (BJPs) are the major pathogenic factor causing cast nephropathy ("myeloma kidney") by coaggregation with Tamm-Horsfall glycoprotein (THP). Understanding the interaction between these proteins is therefore important in developing treatment strategies to prevent renal failure from cast formation in multiple myeloma. We developed an enzyme-linked immunoassay to examine this phenomenon. Five different human BJPs (four kappa and one lambda immunoglobulin light chains) were used in this assay that demonstrated these proteins bound THP with different affinity. BJPs competed among themselves for binding to THP. The binding site was a peptide portion of THP since these proteins also bound deglycosylated THP. Also, one monoclonal antibody directed against a peptide segment of human THP prevented binding of THP to BJPs. By altering the conformation of THP, reducing agents decreased binding between these two proteins in concentration-dependent fashion. In turbidity studies, the monoclonal antibody that prevented binding and a reducing agent, dithiothreitol, decreased coaggregation. Deglycosylated THP did not coaggregate with BJPs. We concluded that ionic interaction between BJPs and a specific peptide binding site on THP promoted heterotypic coaggregation. The carbohydrate moiety of THP was also essential for coaggregation, perhaps by facilitating homotypic aggregation of THP.
Huang
Z Q
ZQ
Department of Medicine, University of Alabama at Birmingham 35292-0007.
Kirk
K A
KA
Connelly
K G
KG
Sanders
P W
PW
D001536:Bence Jones Protein / Q000302:isolation & purification / Q000378:metabolism* / Q000652:urine; D001665:Binding Sites; D001667:Binding, Competitive; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism; D007146:Immunoglobulin lambda-Chains / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009088:Mucoproteins / Q000302:isolation & purification / Q000378:metabolism* / Q000652:urine; D009101:Multiple Myeloma / Q000652:urine; D009391:Nephelometry and Turbidimetry; D010396:Penicillamine / Q000494:pharmacology; D051437:Renal Insufficiency / Q000652:urine; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013997:Time Factors; D058949:Uromodulin
D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D009088:Mucoproteins; D013438:Sulfhydryl Compounds; C548612:UMOD protein, human; D058949:Uromodulin; D001536:Bence Jones Protein; D010396:Penicillamine