NMR structure and mutagenesis of the FADD (Mort1) death-effector domain View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1998-04

AUTHORS

Matthias Eberstadt, Baohua Huang, Zehan Chen, Robert P. Meadows, Shi-Chung Ng, Lixin Zheng, Michael J. Lenardo, Stephen W. Fesik

ABSTRACT

When activated, membrane-bound receptors for Fas and tumour-necrosis factor initiate programmed cell death by recruiting the death domain of the adaptor protein FADD to the membrane. FADD then activates caspase 8 (also known as FLICE or MACH) through an interaction between the death-effector domains of FADD and caspase 8. This ultimately leads to the apoptotic response. Death-effector domains and homologous protein modules known as caspase-recruitment domains have been found in several proteins and are important regulators of caspase (FLICE) activity and of apoptosis. Here we describe the solution structure of a soluble, biologically active mutant of the FADD death-effector domain. The structure consists of six antiparallel, amphipathic alpha-helices and resembles the overall fold of the death domains of Fas and p75. Despite this structural similarity, mutations that inhibit protein-protein interactions involving the Fas death domain have no effect when introduced into the FADD death-effector domain. Instead, a hydrophobic region of the FADD death-effector domain that is not present in the death domains is vital for binding to FLICE and for apoptotic activity. More... »

PAGES

941

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/31972

DOI

http://dx.doi.org/10.1038/31972

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1008979929

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/9582077


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