The Structure of FADD and Its Mode of Interaction with Procaspase-8

Paul E. Carrington, Cristinel Sandu, Yufeng Wei, Justine M. Hill, Gaku Morisawa, Ted Huang, Evripidis Gavathiotis, Yu Wei, Milton H. Werner

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

The structure of FADD has been solved in solution, revealing that the death effector domain (DED) and death domain (DD) are aligned with one another in an orthogonal, tail-to-tail fashion. Mutagenesis of FADD and functional reconstitution with its binding partners define the interaction with the intracellular domain of CD95 and the prodomain of procaspase-8 and reveal a self-association surface necessary to form a productive complex with an activated "death receptor." The identification of a procaspase-specific binding surface on the FADD DED suggests a preferential interaction with one, but not both, of the DEDs of procaspase-8 in a perpendicular arrangement. FADD self-association is mediated by a "hydrophobic patch" in the vicinity of F25 in the DED. The structure of FADD and its functional characterization, therefore, illustrate the architecture of key components in the death-inducing signaling complex.

Original languageEnglish (US)
Pages (from-to)599-610
Number of pages12
JournalMolecular Cell
Volume22
Issue number5
DOIs
StatePublished - Jun 9 2006
Externally publishedYes

Fingerprint

Caspase 8
Death Domain Receptor Signaling Adaptor Proteins
Death Domain Receptors
Mutagenesis
Death Effector Domain

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Carrington, P. E., Sandu, C., Wei, Y., Hill, J. M., Morisawa, G., Huang, T., ... Werner, M. H. (2006). The Structure of FADD and Its Mode of Interaction with Procaspase-8. Molecular Cell, 22(5), 599-610. https://doi.org/10.1016/j.molcel.2006.04.018

The Structure of FADD and Its Mode of Interaction with Procaspase-8. / Carrington, Paul E.; Sandu, Cristinel; Wei, Yufeng; Hill, Justine M.; Morisawa, Gaku; Huang, Ted; Gavathiotis, Evripidis; Wei, Yu; Werner, Milton H.

In: Molecular Cell, Vol. 22, No. 5, 09.06.2006, p. 599-610.

Research output: Contribution to journalArticle

Carrington, PE, Sandu, C, Wei, Y, Hill, JM, Morisawa, G, Huang, T, Gavathiotis, E, Wei, Y & Werner, MH 2006, 'The Structure of FADD and Its Mode of Interaction with Procaspase-8', Molecular Cell, vol. 22, no. 5, pp. 599-610. https://doi.org/10.1016/j.molcel.2006.04.018
Carrington PE, Sandu C, Wei Y, Hill JM, Morisawa G, Huang T et al. The Structure of FADD and Its Mode of Interaction with Procaspase-8. Molecular Cell. 2006 Jun 9;22(5):599-610. https://doi.org/10.1016/j.molcel.2006.04.018
Carrington, Paul E. ; Sandu, Cristinel ; Wei, Yufeng ; Hill, Justine M. ; Morisawa, Gaku ; Huang, Ted ; Gavathiotis, Evripidis ; Wei, Yu ; Werner, Milton H. / The Structure of FADD and Its Mode of Interaction with Procaspase-8. In: Molecular Cell. 2006 ; Vol. 22, No. 5. pp. 599-610.
@article{4085b049e01649be8251ed40533f1169,
title = "The Structure of FADD and Its Mode of Interaction with Procaspase-8",
abstract = "The structure of FADD has been solved in solution, revealing that the death effector domain (DED) and death domain (DD) are aligned with one another in an orthogonal, tail-to-tail fashion. Mutagenesis of FADD and functional reconstitution with its binding partners define the interaction with the intracellular domain of CD95 and the prodomain of procaspase-8 and reveal a self-association surface necessary to form a productive complex with an activated {"}death receptor.{"} The identification of a procaspase-specific binding surface on the FADD DED suggests a preferential interaction with one, but not both, of the DEDs of procaspase-8 in a perpendicular arrangement. FADD self-association is mediated by a {"}hydrophobic patch{"} in the vicinity of F25 in the DED. The structure of FADD and its functional characterization, therefore, illustrate the architecture of key components in the death-inducing signaling complex.",
keywords = "CELLCYCLE",
author = "Carrington, {Paul E.} and Cristinel Sandu and Yufeng Wei and Hill, {Justine M.} and Gaku Morisawa and Ted Huang and Evripidis Gavathiotis and Yu Wei and Werner, {Milton H.}",
year = "2006",
month = "6",
day = "9",
doi = "10.1016/j.molcel.2006.04.018",
language = "English (US)",
volume = "22",
pages = "599--610",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - The Structure of FADD and Its Mode of Interaction with Procaspase-8

AU - Carrington, Paul E.

AU - Sandu, Cristinel

AU - Wei, Yufeng

AU - Hill, Justine M.

AU - Morisawa, Gaku

AU - Huang, Ted

AU - Gavathiotis, Evripidis

AU - Wei, Yu

AU - Werner, Milton H.

PY - 2006/6/9

Y1 - 2006/6/9

N2 - The structure of FADD has been solved in solution, revealing that the death effector domain (DED) and death domain (DD) are aligned with one another in an orthogonal, tail-to-tail fashion. Mutagenesis of FADD and functional reconstitution with its binding partners define the interaction with the intracellular domain of CD95 and the prodomain of procaspase-8 and reveal a self-association surface necessary to form a productive complex with an activated "death receptor." The identification of a procaspase-specific binding surface on the FADD DED suggests a preferential interaction with one, but not both, of the DEDs of procaspase-8 in a perpendicular arrangement. FADD self-association is mediated by a "hydrophobic patch" in the vicinity of F25 in the DED. The structure of FADD and its functional characterization, therefore, illustrate the architecture of key components in the death-inducing signaling complex.

AB - The structure of FADD has been solved in solution, revealing that the death effector domain (DED) and death domain (DD) are aligned with one another in an orthogonal, tail-to-tail fashion. Mutagenesis of FADD and functional reconstitution with its binding partners define the interaction with the intracellular domain of CD95 and the prodomain of procaspase-8 and reveal a self-association surface necessary to form a productive complex with an activated "death receptor." The identification of a procaspase-specific binding surface on the FADD DED suggests a preferential interaction with one, but not both, of the DEDs of procaspase-8 in a perpendicular arrangement. FADD self-association is mediated by a "hydrophobic patch" in the vicinity of F25 in the DED. The structure of FADD and its functional characterization, therefore, illustrate the architecture of key components in the death-inducing signaling complex.

KW - CELLCYCLE

UR - http://www.scopus.com/inward/record.url?scp=33744539048&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33744539048&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2006.04.018

DO - 10.1016/j.molcel.2006.04.018

M3 - Article

C2 - 16762833

AN - SCOPUS:33744539048

VL - 22

SP - 599

EP - 610

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 5

ER -