The amino acid sequence of “heavy chain disease” protein ZUC. Structure of the Fc fragment of immunoglobulin G3

Wolfenstein‐Todel, Carlota; Frangione, Blas; Prelli, Frances

doi:10.1016/0006-291x(76)90741-5

Cited by 36 publications

(16 citation statements)

References 13 publications

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“…The amino acid sequence deduced from the OMM cDNA agrees with published y3 protein sequences (21,22) with the exception of seven residues. Positions 283 and 386 involve Glu/ Gln interchanges which probably reflect uncertainties in the protein sequence.…”

supporting

confidence: 64%

gamma Heavy chain disease in man: cDNA sequence supports partial gene deletion model.

Alexander¹,

Steinmetz²,

Barritault³

et al. 1982

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

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Human y heavy chain disease (HCD) is characterized by the presence in serum of a short monoclonal Ig y chain unattached to light chains. Although most HCD proteins have internal deletions, in some the defect is NH2-terminal. The OMM v3 HCD serum protein is of the latter type, having undergone an extensive NH2-terminal deletion with a sequence starting within the hinge. A cell line synthesizing the OMM protein has enabled us to study the biogenesis ofthe abnormal molecule. In vitro translation ofisolated mRNA yields a protein containing a hydrophobic NH2-terminal leader sequence. In the intact cell, the precursor molecule is processed normally to yield a protein with an NH2-terminal sequence homologous to the beginning of the variable (V) region. The nucleotide sequence of cDNA prepared from the OMM mRNA encodes a 19-amino acid leader followed by the first 15 residues ofthe V region. An extensive internal deletion encompasses the remainder of the V and the entire CHI domain. Immediately following the short V region, there is information in the cDNA for the entire normal hinge. The primary synthetic product is thus an internally deleted molecule that undergoes postsynthetic degradation to yield the NH2-terminally deleted serum protein.The structure of the OMM mRNA suggests that the protein abnormality results from a partial gene deletion rather than defective splicing.In heavy chain disease (HCD), a naturally occurring human lymphoproliferative disorder, variant monoclonal Ig heavy (H) chain fragments are found in the patients' serum or urine. HCD proteins of the 'y class have been studied in detail, although those ofthe a and. y classes have also been described (1, 2). The abnormal serum proteins of the y class all show complete deletion of the CHi domain of the constant (C) region. Additional features separate the proteins into three types. Most ofthe variant molecules studied to date have a normal or aberrant NH2-terminal variable (V)-region sequence ofvariable size, followed by an extensive internal deletion encompassing most of the V region and the CHL domain. Normal structure usually resumes at the beginning ofthe hinge. In the second group, the deletion continues through the hinge, with normal sequence starting in the CH2 domain. Least frequently, y HCD proteins are found that lack the entire V and CHI domains. In such cases, the serum protein sequence starts within the hinge, and it is therefore unclear whether the molecules are of degradative or synthetic origin.A y3 HCD protein was isolated from the serum of patient OMM and shown to have a monomeric molecular weight of 40,000 and an unblocked NH2 terminus (3). It had undergone an extensive NH2-terminal deletion with a homogeneous sequence starting within the hinge. In addition to the HCD protein, the patient's serum also contained a homogeneous (y3)2A2 molecule with apparently normal H and light (L) chains (4). Because the HCD protein was NH2-terminally deleted, it was not possible to tell whether it was the product of partial proteolytic degrad...

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supporting

confidence: 64%

gamma Heavy chain disease in man: cDNA sequence supports partial gene deletion model.

Alexander¹,

Steinmetz²,

Barritault³

et al. 1982

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

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“…We therefore compared the deduced aminoacid of this gene with the G3m(b) y3 WIS (33) and ZUC (34), as well as with the G3m (g=gl,g5) and Gm(u,v) 0MM (29) proteins and with the two \/3 myeloma proteins carrying allotypic specificities found primarily in mongoloid populations: GOE, G3m…”

Section: 8mentioning

confidence: 99%

Sequence of a human immunoglobulin gamma 3 heavy chain constant region gene: comparison with the other human C_γgenes

et al. 1986

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We report the first and complete nucleotide sequence of a human gamma 3 heavy chain constant region gene (Cy3). This gene displays the same organization than the others Cy genes and exhibits normal RNA splice and polyadenylation sites. A comparison of its primary sequence with those of Cy 1, Cy2 and Cy4 genes confirms the high degree of homology (95%) of the human family in both coding and non-coding regions, and the divergence of the hinge region. The Cy3 gene we sequenced codes for a Gm(b) y3 chain (EZZ).Comparison with other known protein sequences reveals that only two specific aminoacids are involved in the Gm(b) and Gm(g) allotypes, which suggests an important part of the spatial configuration in the allotypic specificities.

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“…An interesting observation related to the possible role of hydrophobic interactions to Protein A-IgG binding is the lack of binding between human IgG 3 of the s 2 t 2 allotype while the allotype s þ t þ does bind to Protein A. The difference in binding behavior can be attributed to a single amino acid substitution of histidine (s þ t þ ) for an arginine residue (s 2 t 2 ) at position 435 of the heavy chain of the IgG 3 (Wolfenstein-Todel et al 1976;Michaelsen et al 1977;Haake et al 1982). It does appear that the driving forces of the interaction between the Fc fragment of IgG and Protein A are mainly hydrophobic interactions.…”

Section: Macromolecular Affinity Ligandsmentioning

confidence: 95%

Affinity Chromatographic Purification of Antibodies

2007

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Affinity chromatographic methods for purifying antibodies are reviewed. Topics reviewed include (a) the matrices used in the preparation of the affinity supports; (b) the chemistries commonly used to attach affinity ligands directly on hydroxyl-carrying supports and indirectly through the use of bifunctional agents to crosslink the affinity ligands to the supports; (c) methods for detecting ligand leakage; (d) macromolecular affinity ligands; (e) low molecular weight peptidyl affinity ligands; (f) low molecular weight non-peptidyl affinity ligands; (g) optimal conditions for achieving improved product yield; and (h) optimal elution systems that minimize the denaturation of the purified antibodies.

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The amino acid sequence of “heavy chain disease” protein ZUC. Structure of the Fc fragment of immunoglobulin G3

Cited by 36 publications

References 13 publications

gamma Heavy chain disease in man: cDNA sequence supports partial gene deletion model.

gamma Heavy chain disease in man: cDNA sequence supports partial gene deletion model.

Sequence of a human immunoglobulin gamma 3 heavy chain constant region gene: comparison with the other human C_γgenes

Affinity Chromatographic Purification of Antibodies

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The amino acid sequence of “heavy chain disease” protein ZUC. Structure of the Fc fragment of immunoglobulin G3

Cited by 36 publications

References 13 publications

gamma Heavy chain disease in man: cDNA sequence supports partial gene deletion model.

gamma Heavy chain disease in man: cDNA sequence supports partial gene deletion model.

Sequence of a human immunoglobulin gamma 3 heavy chain constant region gene: comparison with the other human Cγgenes

Affinity Chromatographic Purification of Antibodies

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Product

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Sequence of a human immunoglobulin gamma 3 heavy chain constant region gene: comparison with the other human C_γgenes