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RIP death domain structural interactions implicated in TNF‐mediated proliferation and survival
Author(s) -
Thakar Juilee,
Schleinkofer Karin,
Borner Christoph,
Dandekar Thomas
Publication year - 2006
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20895
Subject(s) - tradd , death domain , signal transducing adaptor protein , microbiology and biotechnology , apoptosis , biology , signal transduction , receptor , ripk1 , programmed cell death , genetics , necroptosis
Death domain (DD)–containing proteins are involved in both apoptosis and survival/proliferation signaling induced by activated death receptors. Here, a phylogenetic and structural analysis was performed to highlight differences in DD domains and their key regulatory interaction sites. The phylogenetic analysis shows that receptor DDs are more conserved than DDs in adaptors. Adaptor DDs can be subdivided into those that activate or inhibit apoptosis. Modeling of six homotypic DD interactions involved in the TNF signaling pathway implicates that the DD of RIP (Receptor interacting protein kinase 1) is capable of interacting with the DD of TRADD (TNFR1‐associated death domain protein) in two different, exclusive ways: one that subsequently recruits CRADD (apoptosis/inflammation) and another that recruits NFκB (survival/proliferation). Proteins 2006. © 2006 Wiley‐Liss, Inc.