1A1Z

FADD DEATH EFFECTOR DOMAIN, F25G MUTANT, NMR MINIMIZED AVERAGE STRUCTURE

Summary for 1A1Z

• Entry DOI: 10.2210/pdb1a1z/pdb
• Descriptor: FADD PROTEIN (1 entity in total)
• Functional Keywords: apoptosis, death effector domain
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 10545.07

Authors

Eberstadt, M.,Huang, B.,Chen, Z.,Meadows, R.P.,Ng, C.,Fesik, S.W. (deposition date: 1997-12-18, release date: 1998-12-30, Last modification date: 2024-05-22)

Primary citation

Eberstadt, M.,Huang, B.,Chen, Z.,Meadows, R.P.,Ng, S.C.,Zheng, L.,Lenardo, M.J.,Fesik, S.W.
NMR structure and mutagenesis of the FADD (Mort1) death-effector domain.
Nature, 392:941-945, 1998

PubMed 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.

PubMed: 9582077
DOI: 10.1038/31972

Experimental method

SOLUTION NMR