Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been observed that monoclonal immunoglobulin proteins of the lambda VI subgroup have a high propensity to form amyloid deposits. To ascertain whether lambda VI proteins have unique structure determinants that would account for self association and resultant fibril formation, we have determined the complete amino acid sequence of the AL amyloid protein WLT. This protein, isolated from the spleen of a patient with AL amyloid, has 134 amino acid residues and contains the entire variable region, the joining segment, and the first tryptic peptide of the constant region. Comparison of the structure of this protein with the 3 completely sequenced lambda VI proteins reveals that they are highly homologous and contain a 2-residue insertion at positions 68 and 69. Phylogenetic comparisons of the variable domain of all lambda VI proteins reveal that the 3 amyloid proteins WLT, SUT, and AR are all more closely related to each other than to the myeloma protein NIG48. Separating the variable domains into framework (FR) and complementarity-determining regions (CD) and recalculating the phylogenetic comparisons, we identify major substitutions in the FR regions of NIG48 in relation to the amyloid proteins. This supports the hypothesis that the formation of AL amyloid is a result of the secondary structure of the FR regions of the precursor molecules.
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PMID:Amino acid sequence of a lambda VI primary (AL) amyloid protein (WLT). 408 39

To ascertain if lambda VI light chains have unique structural features that account for the preferential association of these proteins with primary or multiple myeloma-related amyloidosis (amyloidosis AL) we have determined the complete amino acid sequence of the variable (V) region of the lambda VI Bence Jones protein SUT. This protein, obtained from a patient with amyloidosis AL, represents a complete light chain consisting of 216 residues and it has structural and serologic properties characteristic for lambda VI light chains. The sequence of the joining segment (J) (positions 100 to 111) of protein SUT is identical to that of the J lambda I segment of the mouse IG lambda light chain gene. V region SUT is closely homologous in sequence to that of another lambda VI amyloid fibrillar protein, AR, differing by 21 residues. The V regions of proteins SUT and AR contain a two-residue insertion at positions 68 and 69 that has also been found in two other lambda VI human light chains but not in the lambda-chains of other V region subgroups.
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PMID:Primary structure of the variable region of a human lambda VI light chain: Bence Jones protein SUT. 641 73

An antiserum prepared against a lambda-Bence Jones protein from a patient (SUT) who had multiple myeloma and amyloidosis had specificity for lambda-light chains of the chemically defined variable (V) region lambda-chain subgroup lambda VI. Sequence analyses of protein SUT and of five other lambda-light chains recognized immunologically as of the V lambda VI subgroup revealed that all six proteins had the N-terminal sequence characteristic for prototype lambda VI proteins. The isotypic nature of the V lambda VI subgroup was demonstrated immunochemically: lambda VI molecules were detected among light chains isolated from the IgG proteins of each of 12 normal individuals and lambda VI antigenic determinants were also detectable on the intact IgG proteins. The frequency of lambda VI molecules among lambda-type light chains is estimated to be approximately 5% based on the finding that 5 of 91 lambda Bence Jones proteins were of the V lambda VI subgroup. Proteins of the V lambda VI subgroup, in contrast to those of the other five chemically-classified lambda chain subgroup, appear to be preferentially associated with the amyloid process as evidenced by the fact that all six lambda VI proteins were obtained from patients with amyloidosis AL and, in addition, 5 of 42 lambda-type monoclonal immunoglobulins from patients with primary or myeloma-associated amyloidosis were classified by immunodiffusion analyses as having lambda VI-type light chains.
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PMID:Bence Jones proteins and light chains of immunoglobulins. Preferential association of the V lambda VI subgroup of human light chains with amyloidosis AL (lambda). 680 27