Cysteine-rich Domain 1 of CD40 Mediates Receptor Self-assembly

Smulski, Cristian R.; Beyrath, Julien; Décossas, Marion; Chekkat, Neila; Wolff, Philippe; Estieu-Gionnet, Karine; Guichard, Gilles; Speiser, Daniel E.; Schneider, Pascal; Fournel, Sylvie

doi:10.1074/jbc.m112.427583

Cited by 33 publications

(31 citation statements)

References 26 publications

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“…Conversely, CRD2-4-binding mAbs display antagonistic activity by possibly disrupting these pre-formed dimers (Yu et al, 2018). Pre-formed CD40 dimers have been shown to assemble via the pre-ligand assembly domain (PLAD) in CRD1 (Smulski et al, 2013). PLAD is also found in CRD1 of other TNFRSF members, including TNFR1, TNFR2, and Fas (Chan et al, 2000;Papoff et al, 1999;Siegel et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Ligand-Blocking and Membrane-Proximal Domain Targeting Anti-OX40 Antibodies Mediate Potent T Cell-Stimulatory and Anti-Tumor Activity

Zhang

Wei

et al. 2019

Cell Reports

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Section: Discussionmentioning

confidence: 99%

Ligand-Blocking and Membrane-Proximal Domain Targeting Anti-OX40 Antibodies Mediate Potent T Cell-Stimulatory and Anti-Tumor Activity

Zhang

Wei

et al. 2019

Cell Reports

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“…In contrast to TNFR1, the crystal structure of CD40 bound to CD40L indicates that each CD40L trimer binds not two, but three, receptors [190]. However, given that CD40 forms ligand-independent homodimers [191], trimers of CD40L may bind two dimers of CD40, and induce formation of oligomeric receptor ligand complexes (Figure 3). Upon CD40 ligation by CD40L, CD40 binds to TRAF proteins.…”

Section: Cd40 Signaling To Nf-κbmentioning

confidence: 99%

Regulation of NF-κB by TNF family cytokines

Hayden

Ghosh

2014

Seminars in Immunology

896

645

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The NF-κB family of inducible transcription factors is activated in response to a variety of stimuli. Amongst the best-characterized inducers of NF-κB are members of the TNF family of cytokines. Research on NF-κB and TNF have been tightly intertwined for more than 25 years. Perhaps the most compelling examples of the interconnectedness of NF-κB and the TNF have come from analysis of knock-out mice that are unable to activate NF-kB. Such mice die embryonically, however, deletion of TNF or TNFR1 can rescue the lethality thereby illustrating the important role of NF-κB as the key regulator of transcriptional responses to TNF. The physiological connections between NF-κB and TNF cytokines are numerous and best explored in articles focusing on a single TNF family member. Instead, in this review, we explore general mechanisms of TNF cytokine signaling, with a focus on the upstream signaling events leading to activation of the socalled canonical and noncanonical NF-κB pathways by TNFR1 and CD40 respectively.

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“…The implications of this go beyond the TNF receptor superfamily and we believe will also apply to any receptor that clusters on the cell surface and is activated by membrane bound ligands. Ligand-free TNFRSF receptors have been shown to form two different dimers [18,19]. One form is a parallel dimer in which the receptors are in a head-to-head arrangement, meaning that the two N-terminals line up next to each other on one end and the C-terminals on the other.…”

Section: Receptors and Ligands Need To Cluster In A Highly Ordered Mamentioning

confidence: 99%

On the TRAIL of Better Therapies: Understanding TNFRSF Structure-Function

Vanamee

Faustman

2020

Cells

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Tumor necrosis factor (TNF) superfamily ligands show diverse biological functions, such as the induction of apoptotic cell death or cell survival and proliferation, making them excellent therapeutic targets for cancer and autoimmunity. We review the latest literature on TNF receptor superfamily signaling with a focus on structure-function. Using combinatorics, we argue that receptors that cluster on the cell surface and are activated by membrane-bound ligands need to arrange in a highly ordered manner, as the probability of random ligand and receptor arrangements matching up for receptor activation is very low. A growing body of evidence indicates that antiparallel receptor dimers that sequester the ligand binding site cluster on the cell surface, forming a hexagonal lattice. Upon ligand binding, this arrangement puts the activated receptors at the right distance to accommodate the downstream signaling partners. The data also suggest that the same geometry is utilized regardless of receptor type. The unified model provides important clues about TNF receptor signaling and should aid the design of better therapies for cancer and various immune mediated diseases.

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Cysteine-rich Domain 1 of CD40 Mediates Receptor Self-assembly

Cited by 33 publications

References 26 publications

Ligand-Blocking and Membrane-Proximal Domain Targeting Anti-OX40 Antibodies Mediate Potent T Cell-Stimulatory and Anti-Tumor Activity

Ligand-Blocking and Membrane-Proximal Domain Targeting Anti-OX40 Antibodies Mediate Potent T Cell-Stimulatory and Anti-Tumor Activity

Regulation of NF-κB by TNF family cytokines

On the TRAIL of Better Therapies: Understanding TNFRSF Structure-Function

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