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)

The digestion of a human IgG1 K myeloma protein with pepsin in the presence of 8M-urea was observed to produce a fragment, designated Fb'2, which differed from the products of aqueous peptic digestion and from other characteristic immunoglobulin digestion products. 2. Fragment Fb's was also found when two other IgG1/K proteins were treated similarly. 3. Sedimentation-equilibrium studies showed the mol.wt. of fragment Fb'2 to be 56800. 4. On reduction, two equivalents of each of three peptides were released from fragment Fb's; these were characterized by N- and C-terminal determinations and by amino acid sequencing. 5. Fragment Fb'2 was shown to consist of the constant regions of both light chains, from residue Ile-117 to the C-terminus, and the CH1 domains and hinge region of the heavy chains, from residue Val-113 to residue Met-252, with a gap of five residues within the intrachain disulphide loop, between residues Leu-174 and Tyr-180.
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PMID:Fb'2, a new peptic fragment of human immunoglobulin G. 77 69

The human myeloma protein Boh (gamma 2, lambda) was isolated and completely reduced and aminoethylated. The light chain was obtained by chromatography on Sephadex G-100 in 4 M guanidine HC1. The amino-terminal sequence on the blocked light chain could be determined by automatic sequence degradation after PCAase treatment. Twenty-one peptides were isolated from a tryptic digest and 12 peptides from a chymotryptic digest. The sequence determination on these peptides was performed by automatic sequencing methods. The light chain of Boh protein belongs to the lambda II subgroup. Unique substitutions have been found at position 8 (Arg) and position 62 (Tyr). Furthermore, the Boh light chain has six cysteine residues, the additional (sixth) cysteine being adjacent to the invariable intrachain-S-S linking cysteine at position 91. Sequence comparison of lambda II proteins reveals a high degree of homology emphasizing the biologic significance of the hypervariable region sequences;
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PMID:The primary structure of a human lambda II chain. 80 2

The carbohydrate composition of an human IgM myeloma protein (IgM Du) has been determined. Seventeen homogeneous glycopeptides are described and exhibit a very large microheterogeneity. They appear as two different groups : the first one contains only mannose and N-acetyl glucosamine, while the other contains N-acetyl-glucosamine, mannose, galactose, fucose, and sialic acid in variable amounts. One glycopeptide termed IX1, which contains 6 mannose and 1 N-acetylglucosamine residues is located on the terminal portion of the Fc fragment and its aminoacid sequence has been determined : Tyr-Asx-Val-Ser.
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PMID:[Preparation and characterization of glycopeptides from human monoclonal immunoglobulin]. 81 88

The phosphorylcholine binding mouse myeloma protein McPC 603 has been shown to have tyrosyl residues in its binding sites by the fact that iodination of the protein causes extensive loss of binding activity which can be substantially retained when the protein is iodinated with sites occupied by ligand. Paired label iodination of McPC 603 protein allowed identification of the tyrosine involved and showed the tyrosine to be in the heavy chain. Gel filtration of heavy chain peptides enabled the tyrosyl-containing peptide of interest to be identified as the N-terminal 33 residue peptide in which the only tyrosine is Tyr 33. Thus H chain Tyr 33 was shown to be a contact amino acid residue in the site of McPC 603 protein. These results provide chemical evidence confirming previously reported x-ray crystallographic identification of H chain Tyr 33 in the site of McPC 603 protein.
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PMID:Identification of heavy chain tyrosine 33 in the binding site of myeloma protein McPC 603 by paired label iodination. 81 15

To provide information on the tertiary structure of the antibody molecule we have investigated the luminescent properties of the light polypeptide chain of human immunoglobulins. The fluorescence and phosphorescence yields, spectra, lifetimes, and anisotropies of a large number of homogeneous light chains, i.e., Bence-Jones proteins and light chains derived from myeloma proteins, were measured. No two proteins gave identical tyrosyl or tryptophyl fluorescence spectra in comparative studies on over 75 proteins belonging to the four basic subgroups of kappa chains and of lambda chains. Spectral differences were apparent even among proteins exhibiting more than 85% amino acid sequence identity. The fluorescence yields of tyrosine and tryptophan vaired 10- and 100-fold, respectively; the Stokes' shift of tryptophan ranged from 328 to 365 nm, but that for tyrosine was apparently invariant (305-307nm). Emission as well as excitation spectra showed tyrosyl and tryptophyl redidues interact minimally or not at all. Fluorescence lifetimes of the tyrosyl and tryptophyl contributions were measured spearately, and the apparent natural lifetimes were calculated. Proteins could be grouped in accordance with similarities in fluorescence lifetimes and fluorescence yields; there was no evident relationship between these groupings and the light chain type (kappa or lambda), amino acid sequence, or tryptophan content. Also apparent were individual differences among kappa light chains and among lambda light chains in respect to their tyrosyl and trptophyl phosphorescence spectra and phosphorescence lifetimes. Certain proteins showed an atypical, short-lived tryptophan phosphorescence decay time. Such variance in the luminescent behavior of the tryptophyl residue(s) indicates a conformational interaction between the V and C domains of light chains. Selective proteolytic cleavage of the light chain into VL and CL fragments permitted the comparison to be made of the luminescent properties of the V and C domains with those of the whole protein. The V domain and intact protein have luminescent features in common, whereas the C domain possesses features distinctive from that of the native protein. Data derived from fluorescence anisotropy spectral studies of intact light chains and their VL-related fragments indicate that energy transfer between tryptophyl residues occurs in the C domain. The results of emission spectroscopic measurements performed at 220 and at 77 K indicate that the observed phophorescence of light chains is mainly from a tryptophyl residue contiguous to a disulfide link. The potential for interdomain interaction in light chains is evidenced by the finding that the orientation of the tryptophyl residue(s) in the V domain can influence the tryptophyl-disulfide ling interactions in the C domain; this interaction may account further for the extensive structural diversity of antibody molecules.
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PMID:Luminescence studies on Bence-Jones proteins and light chains of immunoglobulins and their subunits. 82 15

Magnetic-resonance techniques are used to refine the model of the combining site of the Fv fragment of the dinitrophenyl-binding mouse myeloma protein MOPC 315 constructed by Padlan, Davies, Pecht, Givol & Wright (1976) (Cold Spring Harbor Symp. Quant. Biol.41, in the press). Light-absorption studies indicate a dinitrophenyl-tryptophan interaction in the Fv fragment of the type occurring in free solution. The Dnp-aspartate-tryptophan complex is therefore used as a starting point for the n.m.r. (nuclear-magnetic-resonance) analysis of the dinitrophenyl-Fv fragment interaction. Ring-current calculations are used to determine the geometry of the complex. The specificity of complex-formation between dinitrophenyl and tryptophan is confirmed by the lack of ring-current shifts of the dinitrophenyl resonances when tryptophan is replaced by any other aromatic amino acid. Proton n.m.r. difference spectra (at 270MHz), resulting from the addition of a variety of haptens to the Fv fragment, show that the combining site is highly aromatic in nature. Calculations on the basis of ring-current shifts define the geometry of the combining site, which involves a dinitrophenyl ring in van der Waals contact with four aromatic amino acid residues on the protein. The observation of a nuclear Overhauser effect on the H((3)) resonance of the dinitrophenyl ring provides additional constraints on the relative geometry of the H((3)) proton and an aromatic amino acid residue on the Fv fragment. The specificity of the Fv fragment for dinitrophenyl ligands arises from a stacking interaction of the dinitrophenyl ring with tryptophan-93(L), in an ;aromatic box' of essentially tryptophan-93(L), phenylalanine-34(H) and tyrosine-34(L); asparagine-36(L) and tyrosine-34(L) also contribute by forming hydrogen bonds with the nitro groups on the dinitrophenyl ring. The n.m.r. results also confirm that the antibody-hapten reaction may be visualized as a single encounter step. An Appendix shows the method of calculation of ring currents for the four aromatic amino acids and their use in calculating structures.
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PMID:The combining site of the dinitrophenyl-binding immunoglobulin A myeloma protein MOPC 315. 92 44

From collected data on variable region sequences of heavy chains of immunoglobulins, the probability of random associations of any two amino-acid residues in the complementarity-determining segments was computed, and pairs of residues occurring significantly more frequently than expected were selected by computer. Significant associations between Phe 32 and Tyr 33, Phe 32 and Glu 35, and Tyr 33 and Glu 35 were found in six proteins, all of which were mouse myeloma proteins which bound phosphorylcholine (= phosphocholine). From the x-ray structure of McPC603, Tyr 33 and Glu 35 are contacting residues; a seventh phosphorylcholine-binding mouse myeloma protein also contained Phe 32 and Tyr 33 but position 35 had only been determined as Glx and thus this position had not been selected. Met 34 occurred in all seven phosphorylcholine-binding myeoma proteins but was also present at this position in 29 other proteins and thus was not selected; it is seen in the x-ray structure not to be a contacting residue. The role of Phe 32 is not obvious but it could have some conformational influence. A human phosphorylcholine-binding myeloma protien also had Phe, Tyr, and Met at positions 32, 33, and 34, but had Asp instead of Glu at position 35 and showed a lower binding constant. The ability to use sequence data to locate residues in complementarity-determing segments making contact with antigenic determinants and those playing essentially a structural role would contribute substantially to the understanding of antibody specificity.
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PMID:Attempts to locate residues in complementarity-determining regions of antibody combining sites that make contact with antigen. 106 Nov 62

G-myeloma protein is shown to differ by its conformation from the donor immunoglobulin G. It is characterized by a more polar surrounding of the molecule tyrosine and tryptophane residua. Under the effect of urea the changes are less considerable.
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PMID:[Structural peculiarities of protein typical of G-myelomas]. 125 64

To study the expression of HLA-DQ beta chain alleles associated with type 1 diabetes, mAbs were generated from mice immunized with synthetic peptides representing allelic HLA-DQw7 and HLA-DQw8 beta chain sequences. The splenocytes from immunized mice were fused with myeloma cells, either immediately after or following additional in vitro boosting with peptide. Peptide-specific mAbs, predominantly of the IgG isotype, were isolated only from in vitro boosted splenocytes. Immunoblot analysis showed that several of the mAbs cross-reacted with DQ beta chain molecules. One mAb to a peptide representing DQw8 beta position [49-60] specifically recognised the DQw8 beta chain. Three mAbs to a peptide representing DQw8 beta position [39-52] specifically recognised an epitope consisting of Gly-Val-Tyr in position 45-47, i.e., all DQ beta alleles except DQw7 beta (position 45-47: Glu-Val-Tyr) and DQw2 beta (position 45-47; Gly-Glu-Phe). In FACS analysis these mAbs bound lymphocytes with the same specificity as found by immunoblotting analysis. Thus, by combining in vivo and in vitro immunization we have generated a number of epitope specific monoclonal IgG antibodies that distinguish closely related HLA-DQ beta chain alleles in predetermined positions.
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PMID:Production of epitope specific monoclonal IgG antibodies to HLA class II molecules by combining in vivo and in vitro immunization. 137 72

Engagement of the cell surface receptor for interleukin 7 (IL-7R) provokes protein tyrosine phosphorylation, although the receptor lacks a kinase catalytic domain in its cytoplasmic tail. The molecular basis of this response is not known. Here we report that the IL-7R functions by recruiting p59fyn, an intracellular tyrosine kinase of the src family. Treatment of pre-B cells with IL-7 causes an enhancement of the catalytic activity of p59fyn, but not of the related kinase p62yes. IL-7-dependent stimulation of the enzyme phosphatidylinositol 3-kinase, a tyrosine kinase substrate, provides further evidence suggestive of p59fyn activation. We demonstrate that p59fyn forms part of a protein complex with the IL-7R. A chimeric receptor comprising the CD8 extracellular domain and the IL-7R cytoplasmic tail (CD8/IL-7R) recruits tyrosine kinase activity in transfected myeloma cells, and p59fyn can be detected in association with it by immunoprecipitation and immunoblotting. Conversely, p59fyn immunoprecipitates contain the phosphorylated CD8/IL-7R. We have identified a segment of the IL-7R cytoplasmic tail which mediates p59fyn recruitment: a truncated CD8/IL-7R containing only this segment recruits tyrosine kinase activity, associates with p59fyn, and activates phosphatidylinositol 3-kinase. Interestingly, this segment contains no tyrosine residues, although it is the phosphotyrosine-binding src homology domains of p59fyn and phosphatidylinositol 3-kinase which mediate their association with many growth factor receptors. Thus our results suggest that an unusual interaction links IL-7R to these two important signaling pathways.
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PMID:Interleukin 7 receptor functions by recruiting the tyrosine kinase p59fyn through a segment of its cytoplasmic tail. 146 44


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