Three-dimensional structure of an Fv from a human IgM immunoglobulin

Fan, Zhao-chang; Shan, Lin; Guddat, L.W.; He, Xiaomin; Gray, William R.; Raison, Robert L.; Edmundson, Allen B.

doi:10.1016/0022-2836(92)90500-j

Cited by 82 publications

(47 citation statements)

References 42 publications

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“…Two human IgM antibodies, Pot and Mez, contain HCDR3s of 12 and 14 residues, respectively [22,23]. In the Pot Fv, HCDR3 fills all of the available space between VL and VH, while the Mez HCDR3 loop protrudes into the surrounding solvent.…”

Section: Incorporation Of Long Cdr3s Into V Domainsmentioning

confidence: 99%

“…The Pot HCDR3 has the sequence HRVSYVLTGFDS and appears to have collapsed to fill all available space in the VL-VH domain interface, expelling water molecules in the process [22] (fig. 2, 3).…”

Section: Human Igms With Unusual Hcdr3 Conformationsmentioning

confidence: 99%

“…The 2.3 Å X-ray structure of the Pot Fv (PDB code 1IGM) was determined previously [22]. The Pot IgM does not bind to peptides and displays relatively weak binding activity for a range of macromolecules, in a manner associated with polyreactive or natural (auto)antibodies [15,38].…”

Section: Human Igms With Unusual Hcdr3 Conformationsmentioning

confidence: 99%

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Incorporation of Long CDR3s into V Domains: Implications for the Structural Evolution of the Antibody-Combining Site

Ramsland

Kaushik

Marchalonis

et al. 2001

Exp Clin Immunogenet

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Available data suggest that ‘primitive’ antibody-combining sites often include longer than average HCDR3s. Long HCDR3 sequences have been reported in diverse vertebrates, including humans, cattle, camels and sharks. These long HCDR3 segments contain unusual sequence features such as stretches of Gly or Pro residues and multiple Cys residues. We examined how longer than average HCDR3s were accommodated in the V domains of human, murine and camel antibodies with known three-dimensional structures. The main conclusions were that (1) HCDR3s longer than 12 residues should protrude outward from the V domains; (2) descending HCDR3 polypeptides may utilize VL (including LCDR3) constituents as a platform, supporting the protruding segments; (3) intra- and inter-HCDR disulfides are frequently formed to rigidify the structure of HCDR3 or the combining site, and (4) V and C domains were possibly more similar in primordial antibodies than they are in their present day counterparts.

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Section: Incorporation Of Long Cdr3s Into V Domainsmentioning

confidence: 99%

Section: Human Igms With Unusual Hcdr3 Conformationsmentioning

confidence: 99%

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Incorporation of Long CDR3s into V Domains: Implications for the Structural Evolution of the Antibody-Combining Site

Ramsland

Kaushik

Marchalonis

et al. 2001

Exp Clin Immunogenet

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“…In the a, (3, K, and A chains, however, one residue is inserted between the Gly and the Arg or Lys residues believed to be critical for antigenic activity. Clearly, in the K and A chains (30,35) and presumably in the a and (3chains, the Arg or Lys side chain is in an exposed surface position and available for binding to an antibody. The Pot human light (K) chain has a Gly-Pro-Gly sequence like peptide RP142.…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies to the alpha/beta T-cell receptors in human immunodeficiency virus infection: dysregulation and mimicry.

Lake

Schluter

Wang

et al. 1994

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

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AutoImmune reactivity is a consequence of infection with human immunodeficlency virus (HIV). We studied serological cross-reactions of purified pooled IgG from sera of HIV-infected individuals by using nested sets of synthetic overlapping peptides duplicating the covalent srtures of T-cell receptors (TCRs) and immunoglobulin light chains and report that two processes of autoantibody production occur. (i0 IgG autoantibodies to putative regulatory variable domain CDR1 and FR3 epitopes (where CDR is complemen-

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“…The data were checked for systematic absences using the program PARITY (from S. Evans). An initial model was obtained by molecular replacement with AMORE (26), using the coordinates of entry 1IGM in the Protein Data Bank (27,28). The structure was refined with X-PLOR (29), with 8% of the reflections set aside to compute an R free value.…”

Section: Bacterial Strain and Expression-the Construct Was Expressed Inmentioning

confidence: 99%

A Single Chain Fv Fragment of P-glycoprotein-specific Monoclonal Antibody C219

Hoedemaeker

Signorelli

Johns

et al. 1997

Journal of Biological Chemistry

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A construct encoding a single chain variable fragment of the anti-P-glycoprotein monoclonal antibody C219 was made by combining the coding sequences for the heavy and light chain variable domains with a sequence encoding the flexible linker (GGGGS) 3 , an OmpA signal sequence, a c-myc identification tag, and a five-histidine purification tag. The construct was expressed in Escherichia coli and purified from the periplasmic fraction using a nickel chelate column and ion exchange chromatography. Three-step Western blot analysis showed that the construct retains binding affinity for P-glycoprotein. Crystals of 1.0 ؋ 0.2 ؋ 0.2 mm were grown in 100 mM citrate, pH 4.5, 21% polyethylene glycol 6000 in the presence of low concentrations of subtilisin, resulting in proteolytic removal of the linker and purification tags. The structure was solved to a resolution of 2.4 Å with an R factor of 20.6, an R free of 28.5, and good stereochemistry. This result could lead to a clinically useful product based on antibody C219 for the diagnosis of P-glycoprotein-mediated multidrug resistance. The molecule will also be useful in biophysical studies of functional domains of P-glycoprotein, as well as studies of the intact molecule.

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Three-dimensional structure of an Fv from a human IgM immunoglobulin

Cited by 82 publications

References 42 publications

Incorporation of Long CDR3s into V Domains: Implications for the Structural Evolution of the Antibody-Combining Site

Incorporation of Long CDR3s into V Domains: Implications for the Structural Evolution of the Antibody-Combining Site

Autoantibodies to the alpha/beta T-cell receptors in human immunodeficiency virus infection: dysregulation and mimicry.

A Single Chain Fv Fragment of P-glycoprotein-specific Monoclonal Antibody C219

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