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)

Protein A-binding fractions of two IgA1 myeloma proteins failed to produce Fc fragments on digestion with IgA1 protease from Streptococcus sanguis. A polymeric protein A-binding IgA1 fraction yielded a protein A-non-binding monomer, which was further cleaved into Fab fragments but it did not yield Fc fragments. The protein A-binding fraction of a monomeric IgA1 yielded an IgA molecule lacking one Fab fragment. Subsequently, the remaining part of its cleaved alpha chain was degraded. Further digestion yielded Fab but not Fc fragments. Similarly, F(abc)2 and Fabc fragments, which lack the CH3 domain (8), yielded Fab fragments but not CH2 domains. Thus, the enzyme in addition to cleaving IgA in the hinge region, under certain conditions, also degrades its Fc fragments.
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PMID:Cleavage of protein A-binding IgA1 with IgA1 protease from Streptococcus sanguis. 635

Intact rabbit immunoglobulin G molecules (IgGs) and their papain or pepsin fragments were radio-iodinated and injected into HeLa cells. Whole IgGs, Fab2, and Fc fragments were degraded with half-lives of 60-90 h, whereas half-lives of Fab fragments were 110 h. These results indicate that proteolytic cleavage in the hinge region of the IgG molecule is not the rate-limiting step in its intracellular degradation. The hingeless human myeloma protein, Mcg, was degraded at the same rate as bulk human IgG, providing further evidence that the proteolytically susceptible hinge region is not important for intracellular degradation of IgG molecules. SDS acrylamide gel analysis of injected rabbit IgG molecules revealed that heavy and light chains were degraded at the same rate. Injected rabbit IgGs and rabbit IgG fragments were also examined on isoelectric focusing gels. Fab, Fab2, and Fc fragments were degraded without any correlation with respect to isoelectric point. Positively charged rabbit IgGs disappeared more rapidly than their negative counterparts, contrary to the trend reported for normal intracellular proteins. The isoelectric points of two mouse monoclonal antibodies were essentially unchanged after injection into HeLa cells, suggesting that the altered isoelectric profile observed for intact rabbit IgG resulted from degradation and not protein modification. The intracellular distributions of IgG fragments and intact rabbit IgG molecules were determined by autoradiography of thin sections through injected cells. Intact IgG molecules were excluded from HeLa nuclei whereas both Fab and Fc fragments readily entered them. Thus, for some proteins, entry into the nuclear compartment is determined primarily by size.
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PMID:Intracellular distribution and degradation of immunoglobulin G and immunoglobulin G fragments injected into HeLa cells. 640 51

An IgG1K monoclonal component with abnormal covalent H and L chains structure (LIA protein) was identified during a systematic screening of myeloma proteins by means of non-reducing/reducing SDS-polyacrylamide gel electrophoresis. Using immunochemical and immunogenetic analysis the mutation was characterized as a hinge region deletion, with loss of L-H and H-H disulphide bridges and direct L-L bonds. Moreover, non-expression of the G1m(z) allotype suggested that the deletion might start at residue 216, a preferential site previously observed in other HCD proteins. This feature is in agreement with the discontinuous structure of immunoglobulin CH genes and suggests that an abnormal switch mechanism is responsible for the deletion.
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PMID:A new case of gamma-heavy chain disease (LIA protein) with deletion of the hinge region. 642 78

In the previous communication (Mellis, S. J., and Baenziger, J. U. (1983) J. Biol. Chem. 258, 11546-11556), the structures of the oligosaccharides present at the 3 asparagine glycosylation sites of a human IgD myeloma protein were defined. In this communication, we present the structures of the O-glycosidically linked oligosaccharides located in the hinge region of IgD:WAH. Three or four threonine residues and one serine residue in the region bear O-glycosidically linked oligosaccharides. Approximately 50% of these molecules have the structure Gal beta 1 leads to 3 GalNAc which is identical with the structure of the predominant oligosaccharide in the hinge region of human IgA1 myeloma proteins (Baenziger, J. U., and Kornfeld, S. (1974) J. Biol. Chem. 249, 7270-7281). The remainder of the oligosaccharides contain 1 or 2 residues of N-acetylneuraminic acid and have the structures NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc (30%), Gal beta 1 leads to (NeuAc alpha 2 leads to 6)GalNAc (12%), and NeuAc alpha 2 leads to 3Gal beta 1 leads to 3(NeuAc alpha 2 leads to 6)GalNAc (8%). The sialylated molecules have not been encountered previously on other human immunoglobulin heavy chains. These structures, however, have been described on a number of secreted and membrane glycoproteins. Examination of oligosaccharides isolated from different subregions of the IgD hinge indicated that a specific distribution of the sialylated structures among the glycosylated amino acids of the hinge region is not likely.
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PMID:Structures of the O-glycosidically linked oligosaccharides of human IgD. 661 28

The complete amino acid sequence of the 432-residue heavy (alpha) chain of mouse myeloma MOPC 511 has been determined. The variable region of the alpha chain of IgA 511, a phosphocholine-binding protein, is highly homologous to that of the other phosphocholine-binding immunoglobulins. Comparison of the 511 alpha chain constant region with that of other mouse and human heavy chains shows that sequence divain. The CH3 domain disulfide bridge of the 511 alpha chain, for example, consists of only 28 amino acid residues compared to 60 residues for other chains and domains. Sequence divergences are alsos apparent at the CH2/CH3 domain boundary, an area where a number of frameshift mutations have occurred. One mutant, mouse IgA 47A, lacks the entire CH3 domain. Comparison of the 511 alppha chain with the 47A alpha chain reveals two noncconservative amino acid changes at the COOH terminus of the 47A chain, Ser-Gln for VAl-Thr in the 511 chain. These changes and the deletion of the CH3 domain can be explained by a single genetic event--namely, a frameshift mutation followed by premature chain termination. The remainder of the 47A constant region, including the hinge region, is identical to the 511 alpha chain, except for two conservative changes in the CH1 domain: serine-126 and theonine-197 in the 511 alpha chain are both replaced by alanine in the 47A chain.
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PMID:Complete amino acid sequence of a mouse immunoglobulin alpha chain (MOPC 511). 677 28

Two proteolytic enzymes of Pseudomonas aeruginosa--an alkaline protease and an elastase--were incubated with human myeloma proteins IgG and IgA as well as with secretory IgA at 37 degrees C. Digest mixtures were analyzed after 1, 5, 12, 24, 48 and 72 h by SDS-polyacrylamide gel electrophoresis after reduction by 2-mercaptoethanol. Under conditions which resulted in cleavage of all three immunoglobulins by the elastase in the hinge-region, the alkaline protease cleaved only IgA. It was suggested that proteases of PA interfere with the immune-system of the host by cleavage of immunoglobulins. Elastase-positive PA strains should be more virulent compared with PA strains which produce only alkaline protease or are protease-negative at all.
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PMID:[Extracellular toxins of Pseudomonas aeruginosa. II. Effect of two proteases on human immunoglobulins IgG, IgA and secretory IgA (author's transl)]. 679 5

We report here the primary structure of an immunoglobulin heavy chain synthesized by ICR 16, a variant of the MPC 11 mouse myeloma cell line. The ICR 16 heavy chain is a gamma 2b-gamma 2a hybrid, consisting of the CH1 domain of gamma 2b and the hinge, CH2 and CH3 domains of gamma 2a subclasses. The genetic mechanism by which ICR 16 occurred may be recombination, based on homologies in both coding and intervening sequences in gamma 2b and gamma 2a constant region genes. Although the Fc fragment of ICR 16 is completely gamma 2a-like and has been shown to bind to gamma 2a Fc receptors on mouse macrophages, the intact H2L2 molecules is unable to do so. Such an observation underscores the crucial role that conformation may play in the ability of immunoglobulins to carry out biologic functions.
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PMID:Effects of immunoglobulin structure on Fc receptor binding: a mouse myeloma variant immunoglobulin with a gamma 2b-gamma 2a hybrid heavy chain having a complete gamma 2a Fc region fails to bind to gamma 2a Fc receptors on mouse macrophages. 680 75

We have determined the amino acid sequence of the variable (V) region of the delta heavy (H) chain of human IgD isolated from the plasma of myeloma patient WAH. This V region is unusual in its amino end group (arginine) and in its length (129 residues). The length is due to 10 insertions in the third complementarity-determining region (CDR3). A computer search showed that no reported CDR3-joining region (-JH) sequences are identical and that they appear to be unrelated to the constant (C) region sequences of immunoglobulins. The V region sequence together with our previous results for the C region give the complete sequence of the human delta chain WAH, which has 512 amino acid residues and a Mr congruent to 65,000. The human delta chain has four domains (V, C delta 1, C delta 2, and C delta 3) and a long hinge region; by comparison, the mouse delta chain lacks a continuous segment of 135 residues, including half the hinge region and the entire C delta 2 domain. The human and mouse delta chains also differ in the number, kind, and location of GlcN and GalN glycans and probably in conformation and quaternary structure. These and other considerations suggest that there may be multiple forms of both secreted and membrane-bound IgD that differ in size, structure, and function.
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PMID:Complete amino acid sequence of the delta heavy chain of human immunoglobulin D. 680 18

This paper describes an IgA related protein Vla which occurred in the serum and urine of a patient with multiple myeloma. The protein was isolated from urine; it had a molecular mass of 70,000 daltons. It was shown to be a two chain IgA half molecule, consisting of a deleted alpha heavy chain, with a molecular mass of 42,000 daltons, which was disulphide linked to a normal kappa type light chain. Fabc fragments were produced from an unrelated myeloma IgA. These had the same biochemical properties as protein V1a, except for the absence of the disulphide linkage between the deleted heavy chains and the light chains. Protein Vla and the Fabc fragments could both be cleaved by IgA1 protease from Streptococcus sanguis, which indicates the presence of the alpha 1 hinge region. An inventory of its antigenic determinants and their similarity to those of previously characterized F(abc)2 fragments, indicates that protein Vla, like the Fabc fragments, contains the CH1 and CH2 domains, but lacks most of the CH3 domain. The fact that cleavage by IgA1 protease from S. sanguis yields a Fab fragment but fails to yield a CH2 domain demonstrates that cleavage by the enzyme is not only restricted to the Pro227-Thr228 bond in the IgA1 hinge region.
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PMID:IgA1 half molecules in human multiple myeloma and the in vitro production of similar fragments from intact IgA1 molecules. 683 48

Pure secretory immunoglobulin A was isolated from human milk by fractionation in gradients of pH and (NH4)2SO4 concentration followed by gel filtration. The hinge region containing all the O-glycosidically linked oligosaccharides was isolated en bloc after trypsin and pepsin hydrolysis and separated by gel filtration. The mixture of O-glycosidically linked oligosaccharides contained N-acetylneuraminic acid (NeuAc), fucose (Fuc), galactose (Gal), N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc) in the molar ratio of 0.2:0.5:2.5:2:1 respectively. After beta-elimination several oligosaccharides were separated by a combination of ion-exchange chromatography and gel-filtration chromatography. The complete structure of four of these oligosaccharides was determined by methanolysis, methylation and mass spectrometry. The structure of the four oligosaccharides which are linked to serine or threonine residues of the hinge region are as follows: beta-Gal-(1 leads to 3)-GalNAc-ol; alpha-HeuAc-(2 leads to 3)-beta-Gal-(1 leads to 3)-GalNAc-ol; beta-Gal-(1 leads to 3)-[beta-GlcNAc-(1 leads to 6)]-GalNAc-ol; beta-Gal-(1 leads to 3)-[beta-Gal-(1 leads to 4)-beta-GlcNac-(1 leads to 6)]-Gal-NAc-ol. These oligosaccharides are more complex and heterogenous than the oligosaccharides linked to serine residues of the hinge region from myeloma serum immunoglobulin A1.
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PMID:Heterogeneity of the glycans O-glycosidically linked to the hinge region of secretory immunoglobulins from human milk. 721 51


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