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Structural analysis of the amyloidogenic kappa Bence Jones protein (FUR).
Amyloid. 1999 Jun; 6(2):77-88.A

Abstract

Patients with systemic amyloidosis associated with multiple myeloma (AL-amyloidosis) exhibit immunoglobulin light chains and fragments which have been identified as amyloid protein. Since a relatively small proportion of patients with multiple myeloma develop AL-amyloidosis, comparison of the amino acid sequence of the amyloidogenic and non-amyloidogenic immunoglobulin light chains and the structural characterization of the amyloid proteins are required to understand the relationship between structure and amyloidogenicity. We determined the primary structure of a kappa I-type Bence Jones protein obtained from a patient (FUR) who had systemic AL-amyloidosis associated with multiple myeloma. We identified eight amino acid replacements unique to this patient among the amyloidogenic kappa I-light chains, and which are also rare among the known kappa type light chains of humans. Three of these substitutions were within the framework regions and may act to destabilize the structure to promote a putative amyloidogenic conformation. In contrast to light chain fragments in the urine, which were processed in the variable region, mass spectrometric analysis of the fibril proteins isolated from lingual amyloid deposits in this patient, revealed that they were all truncated within the constant region and corresponded to residues 1-125, 1-144, and 1-210. Inspection of the predicted three-dimensional model of this protein suggested that these fragments may be generated by a protease specific for the N-terminal sides of basic amino acids. These findings suggest that amino acid substitutions at highly conserved residues may convert non-amyloidogenic to amyloidogenic immunoglobulin light chain proteins.

Authors+Show Affiliations

Department of Biology, Faculty of Science, Niigata University, Japan.No affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

10439113

Citation

Odani, S, et al. "Structural Analysis of the Amyloidogenic Kappa Bence Jones Protein (FUR)." Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis, vol. 6, no. 2, 1999, pp. 77-88.
Odani S, Komori Y, Gejyo F. Structural analysis of the amyloidogenic kappa Bence Jones protein (FUR). Amyloid. 1999;6(2):77-88.
Odani, S., Komori, Y., & Gejyo, F. (1999). Structural analysis of the amyloidogenic kappa Bence Jones protein (FUR). Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis, 6(2), 77-88.
Odani S, Komori Y, Gejyo F. Structural Analysis of the Amyloidogenic Kappa Bence Jones Protein (FUR). Amyloid. 1999;6(2):77-88. PubMed PMID: 10439113.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural analysis of the amyloidogenic kappa Bence Jones protein (FUR). AU - Odani,S, AU - Komori,Y, AU - Gejyo,F, PY - 1999/8/10/pubmed PY - 1999/8/10/medline PY - 1999/8/10/entrez SP - 77 EP - 88 JF - Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis JO - Amyloid VL - 6 IS - 2 N2 - Patients with systemic amyloidosis associated with multiple myeloma (AL-amyloidosis) exhibit immunoglobulin light chains and fragments which have been identified as amyloid protein. Since a relatively small proportion of patients with multiple myeloma develop AL-amyloidosis, comparison of the amino acid sequence of the amyloidogenic and non-amyloidogenic immunoglobulin light chains and the structural characterization of the amyloid proteins are required to understand the relationship between structure and amyloidogenicity. We determined the primary structure of a kappa I-type Bence Jones protein obtained from a patient (FUR) who had systemic AL-amyloidosis associated with multiple myeloma. We identified eight amino acid replacements unique to this patient among the amyloidogenic kappa I-light chains, and which are also rare among the known kappa type light chains of humans. Three of these substitutions were within the framework regions and may act to destabilize the structure to promote a putative amyloidogenic conformation. In contrast to light chain fragments in the urine, which were processed in the variable region, mass spectrometric analysis of the fibril proteins isolated from lingual amyloid deposits in this patient, revealed that they were all truncated within the constant region and corresponded to residues 1-125, 1-144, and 1-210. Inspection of the predicted three-dimensional model of this protein suggested that these fragments may be generated by a protease specific for the N-terminal sides of basic amino acids. These findings suggest that amino acid substitutions at highly conserved residues may convert non-amyloidogenic to amyloidogenic immunoglobulin light chain proteins. SN - 1350-6129 UR - https://www.unboundmedicine.com/medline/citation/10439113/Structural_analysis_of_the_amyloidogenic_kappa_Bence_Jones_protein__FUR__ L2 - https://www.tandfonline.com/doi/full/10.3109/13506129909007307 DB - PRIME DP - Unbound Medicine ER -