Structures of the extracellular domain of the type I tumor necrosis factor receptor

Naismith, J.H.; Devine, Tracey Q.; Kohno, Tadahiko; Sprang, Stephen R.

doi:10.1016/s0969-2126(96)00134-7

Cited by 143 publications

(108 citation statements)

References 30 publications

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“…A variety of possible ways in which receptors can self-associate has been demonstrated crystallographically for the EPO (43,44) and TNF receptors (45)(46)(47), including the formation of ligand-free parallel and anti-parallel dimers in addition to the traditional dimeric receptor-ligand complex. Each of the observed inter-receptor binding modes might play an important role at different stages of receptor functioning.…”

Section: Discussionmentioning

confidence: 99%

Disabling Receptor Ensembles with Rationally Designed Interface Peptidomimetics

Berezov

Chen

Liu

et al. 2002

Journal of Biological Chemistry

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Members of the erbB family receptor tyrosine kinases (erbB1, erbB2, erbB3, and erbB4) are overexpressed in a variety of human cancers and represent important targets for the structure-based drug design. Homo-and heterodimerization (oligomerization) of the erbB receptors are known to be critical events for receptor signaling. To block receptor self-associations, we have designed a series of peptides derived from potential dimerization surfaces in the extracellular subdomain IV of the erbB receptors (erbB peptides). In surface plasmon resonance (BIAcore) studies, the designed peptides have been shown to selectively bind to the erbB receptor ectodomains and isolated subdomain IV of erbB2 with submicromolar affinities and to inhibit heregulin-in- erbB2 (neu, HER2) is a member of the epidermal growth factor or HER family of tyrosine kinase receptors that also includes erbB1 (EGFR, 1 HER1), erbB3 (HER3), and erbB4 (HER4) (1-4). Overexpression of erbB receptors has been found in many types of human cancer raising the possibility that receptor-directed therapies may be useful as cancer management strategies. Greater expression of erbB2 on transformed cells than on normal epithelial tissues allows selective targeting of tumor cells using various approaches (5-13). A variety of strategies have also been developed for targeting the erbB1 receptor, including monoclonal antibodies, ligand-linked immunotoxins, tyrosine kinase inhibitors, and antisense approaches.Recently, we have reported the design of an anti-erbB2 peptide mimetic, AHNP, derived from the structure of the CDR-H3 loop of the anti-erbB2 monoclonal antibody 4D5 and demonstrated its in vitro and in vivo activities in disabling erbB2 tyrosine kinases similar to the monoclonal antibody (14 -16). We have argued that another interesting approach for disabling erbB receptor activity would be targeting protein-protein interaction surfaces. Because protein-protein interactions play a key role in various mechanisms of cellular growth and differentiation, and viral replication, inhibition of these interactions is a promising novel approach for rational drug design against a wide number of cellular and viral targets (17,18). Synthetic peptides that disrupt protein-protein interactions have been successfully shown to act as inhibitors of HIV-1 protease (19), HIV-1 reverse transcriptase (20), herpes simplex virus ribonucleotide reductase (21), and thymidilate synthase (22). Binding of polypeptide hormones, growth factors, or cytokines to cell surface receptors activates dimerization (oligomerization) of the receptors, which leads to the signal transduction to the interior of the cell (23). Although most of the receptor inhibitors developed to date have been focused on the blockade of receptor-ligand or enzyme-substrate interactions, repression of receptor-receptor interactions that accompany oligomerization might also represent an important target for disabling receptor functioning. This approach has been recently used for the design of peptidic estrogen receptor inhibitors ...

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Section: Discussionmentioning

confidence: 99%

Disabling Receptor Ensembles with Rationally Designed Interface Peptidomimetics

Berezov

Chen

Liu

et al. 2002

Journal of Biological Chemistry

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“…TNF receptors are often viewed as monomers, principally because they appear in this form in crystal structures of ligand-receptor complexes. However, TNF-R1 has also been crystallized as both head-tohead and head-to-tail dimers [45], and there is genetic and experimental evidence that Fas, TNF-R1 and CD40 exist as preformed oligomers within the plasma membrane [46]. Self-association of the receptors depends on an N-terminal pre-ligand association domain (PLAD) that includes the first CRD and that is not directly involved in ligand binding.…”

Section: Structural Features Of the Tnf Receptor Familymentioning

confidence: 99%

The molecular architecture of the TNF superfamily

Bodmer

Schneider

Tschopp

2002

Trends in Biochemical Sciences

806

684

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“…The TNF molecule can induce receptor oligomerization increasing the ligand binding affinity (134). The receptors of TNF (TNFR) can be grouped into three classes: 1) having cytoplasmic death domains, 2) linked to adaptor molecules denominated TNF receptor associated factors (TRAFs), and 3) soluble receptors (135,136).…”

Section: Cross-linking Of Tnf and Tnfr Type I Dependent Pathwaymentioning

confidence: 99%

Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

et al. 2009

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One of the functions of the immune system is to recognize and destroy abnormal or infected cells to maintain homeostasis. This is accomplished by cytotoxic lymphocytes. Cytotoxicity is a highly organized multifactor process. Here, we reviewed the apoptosis pathways induced by the two main cytotoxic lymphocyte subsets, natural killer (NK) cells and CD8 + T cells. In base to recent experimental evidence, we reviewed NK receptors involved in recognition of target-cell, as well as lytic molecules such as perforin, granzymes-A and -B, and granulysin. In addition, we reviewed the Fas-FasL intercellular linkage mediated pathway, and briefly the cross-linking of tumor necrosis factor (TNF) and TNF receptor pathway. We discussed three models of possible molecular interaction between lytic molecules from effector cytotoxic cells and target-cell membrane to induction of apoptosis. Cellular & Molecular Immunology. 2009;6(1):15-25.

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Structures of the extracellular domain of the type I tumor necrosis factor receptor

Cited by 143 publications

References 30 publications

Disabling Receptor Ensembles with Rationally Designed Interface Peptidomimetics

Disabling Receptor Ensembles with Rationally Designed Interface Peptidomimetics

The molecular architecture of the TNF superfamily

Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

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