Structure and developmental expression of the nerve growth factor receptor in the chicken central nervous system

Large, Thomas H.; Weskamp, Gisela; Helder, Judith C.; Radeke, Monte J.; Misko, Thomas P.; Shooter, Eric M.; Reichard, Louis F.

doi:10.1016/0896-6273(89)90179-7

Cited by 170 publications

(77 citation statements)

References 63 publications

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“…The homology among the domains is at most 40-50%, including the conserved Cys residues, with the two Trp residues occurring at position 155 in the fourth domain and at 167 nearer the C-terminus. This domain structure is highly conserved among species (Radeke et al, 1987;Large et al, 1989). Two models for the unfolding of the RED are (1) that the four domains unfold independently, or (2) that the four domains are tightly coupled and unfold as a single cooperative unit.…”

Section: Discussionmentioning

confidence: 99%

“…Two transmembrane proteins contribute to NGF binding and the initiation of signal transduction in NGF-responsive neuronal cells. The low affinity NGF receptor, LNGFR or gp75, was the first receptor protein component characterized (Grob et al, 1985), has an appropriate tissue distribution in the nervous system (Taniuchi et al, 1986;Large et al, 1989), and binds NGF with a Kd around 1 nM (Vale & Shooter, 1985). The LNGFR has a relatively small intracellular domain Radeke et al, 1987) and appears to be necessary but not sufficient to mediate full biologReprint requests to: Kenneth E. Neet, Department of Biological Chemistry, UHSKhicago Medical School, 3333 Green Bay Rd., North Chicago, Illinois 60064 Present address: Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201. ical response (Hempstead et al, 1989;Matsushima & Bogenmann, 1990;Pleasure et al, 1990;Yan et al, 1991).…”

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confidence: 99%

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Spectroscopic and chemical studies of the interaction between nerve growth factor (NGF) and the extracellular domain of the low affinity NGF receptor

Timm

Vissavajjhala²,

Ross³

et al. 1992

Protein Science

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Nerve growth factor (NGF) interacts with a cell surface receptor on responsive neurons to initiate a series of cellular events leading to neuronal survival and/or differentiation. The first step in this process is the binding of NGF to a low affinity and/or a high affinity receptor. In the present report, we have studied the conformation and stability of recombinant receptor extracellular domain (RED) from the human low affinity receptor and the structural basis of its interaction with NGF. Circular dichroism (CD) studies indicate that the RED is primarily random coil in nature with little regular secondary structure. Thermal stability studies have shown that this irregular conformation is a specific structure that can undergo a reversible two-state thermal denaturation with a concomitant fluorescent and C D change. During heating at 100 "C for 15 min, the structure of RED is sufficiently unfolded for a reducing agent, dithiothreitol, to inactivate the receptor toward NGF binding and cross-linking. The complex formation between the RED and NGF has been examined by differential CD measurements, and we have shown that a small, reproducible change in conformation occurs in RED or NGF upon interaction. These results are interpreted in terms of the initiation of NGF cell surface binding and possible modes of signal transduction.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Spectroscopic and chemical studies of the interaction between nerve growth factor (NGF) and the extracellular domain of the low affinity NGF receptor

Timm

Vissavajjhala²,

Ross³

et al. 1992

Protein Science

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“…This juxtamembrane sequence has been completely conserved between human, rat, and chicken p75 genes (38). TRAF6 can also be recruited to the IL-1 receptor through binding to IRAK (IL-1 receptor-associated serine-threonine kinase) (31,39).…”

Section: Association Of Traf6 With the P75 Neurotrophin Receptor 2599mentioning

confidence: 99%

Association of the p75 Neurotrophin Receptor with TRAF6

Khursigara

Orlinick

Chao

1999

Journal of Biological Chemistry

222

188

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In addition to the Trk tyrosine kinase receptors, neurotrophins also bind to a second receptor, p75, a member of the tumor necrosis factor receptor superfamily. Several signaling pathways have been implicated for p75 in the absence of Trk receptors, including induction of NF-B and c-Jun kinase activities and increased production of ceramide. However, to date, the mechanisms by which the p75 receptor initiates intracellular signal transduction have not been defined. Here we report a specific interaction between p75 and TRAF6 (tumor necrosis factor receptor-associated factor-6) after transient transfection in HEK293T cells. The interaction was ligand-dependent and maximal at 100 ng/ml of nerve growth factor (NGF). Other neurotrophins also promoted the association of TRAF6 with p75 but to a lesser extent. The binding of TRAF6 was localized to the juxtamembrane region of p75 by co-immunoprecipitation and Western blotting. To assess the functional significance of this interaction, we have tested responses in cultured Schwann cells that express p75 and TRAF6. An NGF-mediated increase in the nuclear localization of the p65 subunit of NF-B could be blocked by the introduction of a dominant negative form of TRAF6 in Schwann cells. These results indicate that TRAF6 can potentially function as a signal transducer for NGF actions through the p75 receptor.

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“…These residues are found on the third and fourth subdomains of NTR, consistent with deletion studies and the location of ligand-blocking monoclonal antibody epitopes (Welcher et al, 1991;Baldwin et al, 1992;Baldwin & Shooter, 1994). NTRs from three species have been sequenced (Johnson et al, 1986;Radeke et al, 1987;Large et al, 1989;Heuer et al, 1990). Predicted binding site residues Thr 91, Glu 95, Arg 150, Glu 15 1, and Cys 152 are either identical or have very conservative replacements in human, rat, and chicken receptors.…”

Section: Analysis Of Receptor-ligand Interactions By Molecular Dockingmentioning

confidence: 99%

Modeled structure of the 75-kDa neurotrophin receptor

Chapman

Kuntz

1995

Protein Sci.

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Motifs in ligand-binding domains of the neurotrophin (NTR) and lymphotoxin (TNFR-I) receptors define a family of receptors that mediates programmed cell death. We have explored relationships of architecture and function in this family through a molecular model of NTR, also called p75NGFR or LANR. Modeling by homology took advantage of four modular subdomains in the crystal structure of TNFR-I that also occur in NTR. Hypothetical complexes between the model and a ligand structure (for nerve growth factor, NGF) were then examined using docking software. NTR appears to bind in the dimer interface of NGF, making two sets of contacts. NTR subdomains 111 and IV provide the ligand-contact surfaces, in contrast to TNFR, in which subdomains 11 and III contact TNF-6. NTR subdomain I1 appears to have been evolutionarily modified, potentially contributing to an interface between receptor subunits. These and other specific predictions of the model will require experimental confirmation.

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Structure and developmental expression of the nerve growth factor receptor in the chicken central nervous system

Cited by 170 publications

References 63 publications

Spectroscopic and chemical studies of the interaction between nerve growth factor (NGF) and the extracellular domain of the low affinity NGF receptor

Spectroscopic and chemical studies of the interaction between nerve growth factor (NGF) and the extracellular domain of the low affinity NGF receptor

Association of the p75 Neurotrophin Receptor with TRAF6

Modeled structure of the 75-kDa neurotrophin receptor

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