Structural Characterization of the p75 Neurotrophin Receptor: A Stranger in the TNFR Superfamily.
Vitam Horm
; 104: 57-87, 2017.
Article
en En
| MEDLINE
| ID: mdl-28215307
ABSTRACT
Although p75 neurotrophin receptor (p75NTR) was the founding member of the tumor necrosis factor (TNF) receptor superfamily (TNFRSF), it is an atypical TNFRSF protein. p75NTR like TNF-R1 and Fas-R contain an extracellular domain with four cysteine-rich domains (CRD) and a death domain (DD) in the intracellular region. While TNFRSF proteins are activated by trimeric TNFSF ligands, p75NTR forms dimers activated by dimeric neurotrophins that are structurally unrelated to TNFSF proteins. In addition, although p75NTR shares with other members the interaction with the TNF receptor-associated factors to activate the NF-κB and cell death pathways, p75NTR does not interact with the DD-containing proteins FADD, TRADD, or MyD88. By contrast, the DD of p75NTR is able to recruit several protein interactors via a full catalog of DD interactions not described before in the TNFRSF. p75-DD forms homotypic symmetrical DD-DD complexes with itself and with the related p45-DD; forms heterotypic DD-CARD interactions with the RIP2-CARD domain, and forms a new interaction between a DD and RhoGDI. All these features, in addition to its promiscuous interactions with several ligands and coreceptors, its processing by α- and γ-secretases, the dimeric nature of its transmembrane domain and its "special" juxtamembrane region, make p75NTR a truly stranger in the TNFR superfamily. In this chapter, I will summarize the known structural aspects of p75NTR and I will analyze from a structural point of view, the similitudes and differences between p75NTR and the other members of the TNFRSF.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Modelos Moleculares
/
Receptor de Factor de Crecimiento Nervioso
/
Receptores Tipo II del Factor de Necrosis Tumoral
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Vitam Horm
Año:
2017
Tipo del documento:
Article