2001
DOI: 10.1016/s0969-2126(01)00590-1
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Structure of CD40 Ligand in Complex with the Fab Fragment of a Neutralizing Humanized Antibody

Abstract: The structure reveals that 5c8 neutralizes CD40L function by sterically blocking CD40 binding. The antigenic epitope is localized in a region of the surface that is likely to be structurally perturbed as a result of genetic mutations that cause hyper-IgM syndrome. The symmetric trimeric arrangement of the Fab fragments in the complex results in a geometry that facilitates the formation of large clusters of complexes on the cell surface.

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Cited by 45 publications
(49 citation statements)
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“…3G. Similarly sized higher-order structures were observed for Abs in complex with other TNF family proteins, including 5c8 and other human CD40L-binding mAbs, as well as anti-TNF mAbs (27,(32)(33)(34). Confocal microscopy showed that these small soluble complexes can translate into even larger ordered structures on the cell surface, presumably driven by avidity (32).…”
Section: Mechanism Of Action Of Mcd40l Dab-fcsmentioning
confidence: 76%
See 1 more Smart Citation
“…3G. Similarly sized higher-order structures were observed for Abs in complex with other TNF family proteins, including 5c8 and other human CD40L-binding mAbs, as well as anti-TNF mAbs (27,(32)(33)(34). Confocal microscopy showed that these small soluble complexes can translate into even larger ordered structures on the cell surface, presumably driven by avidity (32).…”
Section: Mechanism Of Action Of Mcd40l Dab-fcsmentioning
confidence: 76%
“…The 5c8 IgG 1 (27) was converted to a F(ab9) 2 by incubation with 1% pepsin (Sigma-Aldrich) in 50 mM sodium citrate (pH 3.5) for 5 h at room temperature. The reaction was quenched by adding Tris to a final pH of 8.…”
Section: Generation Of 5c8 Ab Fragmentsmentioning
confidence: 99%
“…The CD154 monomer has a typical TNF family structure, containing a sandwich of two antiparallel ␤-sheets, with a Greek key fold (11,25). The extensive trimerization interface between the subunits is formed mostly by hydrophobic residues.…”
Section: Resultsmentioning
confidence: 99%
“…50 HCV translational inhibitors were also obtained by selecting for RNA aptamers against the viral internal ribosome entry site, where translation starts. 51 Combinatorial RNA therapies for HIV-1 infection may have potential for stem cell-based gene therapy…”
Section: Aptamers For Intracellular Targets Are Being Developedmentioning
confidence: 99%