Spectral changes on binding of oligosaccharides to murine immunoglobulin A myeloma proteins

Jolley, Michael E.; Rudikoff, Stuart; Potter, Michael; Glaudemans, Cornelis P.J.

doi:10.1021/bi00740a015

Cited by 65 publications

(47 citation statements)

References 10 publications

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“…Proteins that bind /3(1 -6)-D-galactan are especially intriguing since they show similar sequences in both their heavy and light chains (10,12,13) . Perhaps the most pertinent to the present study, since they arose in genetically different individuals, are the human monoclonal cold agglutinins and antigamma globulins studied by Kunkel, Capra, and their colleagues (44,45) .…”

Section: Discussionmentioning

confidence: 99%

Structural, functional, and idiotypic characteristics of a phosphorylcholine-binding IgA myeloma protein of C57BL/ka allotype.

Claflin¹,

Rudikoff²,

Potter³

et al. 1975

The Journal of Experimental Medicine

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An IgA phosphorylcholine (PC)-binding myeloma protein with IgCH allotypic determinants different from those of BALB/c mice is characterized. The myeloma, CBPC 2, was induced in the CB-20 strain of mice which is congenic to BALB/c but differs from it by carrying the A15 allotypic determinant of C57BL/ka mice. Sequence analysis of the CBPC 2 light chain through the first hypervariable region, as well as isoelectric point analysis, show that this chain is indistinguishable from that of T15, a PC-binding myeloma protein of BALB/c origin. The heavy chains of CBPC 2 and T15 differ by only two amino acids (positions 14 and 16) through the first hypervariable region. As measured by inhibition of precipitation, both CBPC 2 and T15 have the same specificity for PC, glycerophosphorylcholine, acetylcholine, and choline. In addition, CBPC 2 possesses the binding site-associated idiotypic determinant which is present on T15. However, like normal or induced C57BL/6 anti-PC antibody, it does not possess the nonbinding site idiotypic determinant.

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Section: Discussionmentioning

confidence: 99%

Structural, functional, and idiotypic characteristics of a phosphorylcholine-binding IgA myeloma protein of C57BL/ka allotype.

Claflin¹,

Rudikoff²,

Potter³

et al. 1975

The Journal of Experimental Medicine

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“…The immunoglobulin J539 [a mouse IgA2,K; anti-(1-',6)-/-D-galactan] was isolated and purified as described (5), and pepsin fragments were obtained by using a published procedure (6).…”

Section: Methodsmentioning

confidence: 99%

Crystal structure of galactan-binding mouse immunoglobulin J539 Fab at 4.5-A resolution.

Navia¹,

Segal²,

Padlan³

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

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An electron-density map of the mouse galactan-binding immunoglobulin 1539 (IgA2,K) Fab has been calculated to a resolution of 4.5 A by the method of heavy atom isomorphous replacement with four derivatives. The map has been interpreted with the aid of a com uter program which systematically searched for the best fit between the electrondensity map and the known coordinates of individual immunoglobulin domains. The quaternary structure of J539 Fab at this resolution appears similar to that of another mouse immunoglobulin, IgA2,K Fab, McPC603. The model coordinates for J539 Fab should allow us to proceed directly to a high-resolution structure determination without further heavy atom isomorphous replacement.The crystal structures of three immunoglobulin Fabs have been reported (1-3). One of these, the mouse myeloma protein McPC603, belongs to a class of immunoglobulins that bind specifically to phosphocholine. In this paper, we present the results of.a structural analysis at 4.5-A resolution of a second mouse Fab, the galactan-binding immunoglobulin J539. A molecular model has been constructed with the aid of a computer search procedure used previously in the interpretation of the electron-density map of an intact immunoglobulin (4). The model allows us to describe the quaternary structural interactions between the constituent domains and domain pairs of the J539 Fab and reveals a general similarity to McPC603. MATERIALS AND METHODSThe immunoglobulin J539 [a mouse IgA2,K; anti-(1-',6)-/-D-galactan] was isolated and purified as described (5), and pepsin fragments were obtained by using a published procedure (6). Useful heavy atom derivatives were obtained by soaking J539 Fab crystals in stabilizing solutions with 0.25 mM K2Pt(CNS)6 for 2 weeks, 1 mM K2PtCl4 for 1 week, 0.3 mM K2HgI4 for 2 weeks, and 50 mM KI/1 mM chloramine-T (Eastman Kodak) for 1 week. The iodine-derivatized crystals were washed with fresh stabilizing solution after the soaking period. Unique sets of three-dimensional reflection data to 4.5-A spacings were collected from native and derivative crystals with a Picker FACS-1 diffractometer operated in the T-scan mode and using Cu Ka radiation. The various data sets were placed on the same relative scale, and pseudo temperature factors were applied to correct for differences in intensity fall-off. The K2Pt(CNS)6 derivative was analyzed first, and difference Patterson maps, readily interpretable, revealed one site of substitution (Fig. 1). After preliminary refinement with projection data only, the coordinates and occupancy of the K2Pt(CNS)6 site were used to determine the signs of the centric native protein reflections. These signs were used to examine the K2PtCI4 and K2HgI4 derivatives by difference Fourier analysis. The variables for these three heavy atom derivatives were then subjected to alternating cycles of least squares refinement and phase determination with the three-dimensional data. The resulting phasesThe publication costs of this article were defrayed in part by page charge paym...

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“…One such system being developed in our laboratory consists of antibodies with specificity for/3(1,6)-a-galactan moieties. A number of myeloma proteins demonstrating this specificity were initially characterized in terms of specificity (38,40), idiotypy (41), and primary sequence analysis (10,19). More recently we have generated a series of hybridoma proteins exhibiting the same specificity and have reported complete r chain V region sequences for 10 of these (37).…”

Section: Resultsmentioning

confidence: 99%

Galactan-binding antibodies. Diversity and structure of idiotypes.

Rudikoff¹,

Pawlita²,

Pumphrey³

et al. 1983

The Journal of Experimental Medicine

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A group of eight IgM hybridoma proteins induced with beta(1,6)-D-galactan-containing antigens has been characterized in terms of primary amino acid sequence and idiotype expression. The H chain amino acid sequences reveal very strong homology in the VH segment although several substitutions are seen that suggest the occurrence of somatic mutation in these IgM molecules. Significant sequence variation was observed in CDR-3, the region generated by the D segment, and the two recombination events, VH-D and D-JH. The number of amino acids in this region contributed by the D segment was found to vary from two to six, yet the overall length of CDR-3 was precisely maintained by the addition of amino acids on either side of D during the recombination processes. These additional amino acids are suggested to result from nucleotide addition by repair enzymes. Idiotypic analysis of these proteins, in conjunction with an assessment of the H chain sequences, has permitted an identification of the molecular basis of both cross-reacting and unique idiotypic determinants expressed by these molecules.

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Spectral changes on binding of oligosaccharides to murine immunoglobulin A myeloma proteins

Cited by 65 publications

References 10 publications

Structural, functional, and idiotypic characteristics of a phosphorylcholine-binding IgA myeloma protein of C57BL/ka allotype.

Structural, functional, and idiotypic characteristics of a phosphorylcholine-binding IgA myeloma protein of C57BL/ka allotype.

Crystal structure of galactan-binding mouse immunoglobulin J539 Fab at 4.5-A resolution.

Galactan-binding antibodies. Diversity and structure of idiotypes.

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