HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 36, 31974-31980, September 9, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/36/31974    most recent M506938200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sandu, C. Articles by Werner, M. H. Search for Related Content PubMed PubMed Citation Articles by Sandu, C. Articles by Werner, M. H. Social Bookmarking                      What's this?

A Mechanism for Death Receptor Discrimination by Death Adaptors^*

Cristinel Sandu, Evripidis Gavathiotis, Ted Huang, Iga Wegorzewska, and Milton H. Werner

From the Laboratory of Molecular Biophysics, The Rockefeller University, New York, New York 10021

The death domain and death effector domain are two common motifs that mediate protein-protein interactions between components of cell death signaling complexes. The mechanism by which these domains engage their binding partners has been explored by extensive mutagenesis of two death adaptors, FADD and TRADD, suggesting that a death adaptor can discriminate its intended binding partners from other proteins harboring similar motifs. Death adaptors are found to utilize one of two topologically conserved surfaces for protein-protein interaction, whether that partner is another adaptor or its cognate receptor. These surfaces are topologically related to the interaction between death domains observed in the x-ray crystal structure of the Drosophila adaptor Tube bound to Pelle kinase. Comparing the topology of protein-protein interactions for FADD complexes to TRADD complexes reveals that FADD uses a Tube-like surface in each of its death motifs to engage either CD95 or TRADD. TRADD reverses these roles, employing a Pelle-like surface to interact with either receptor TNFR1 or adaptor FADD. Since death adaptors display a Tube-like or Pelle-like preference for engaging their binding partners, Tube/Pelle-like pairing provides a mechanism for death adaptor discrimination of death receptors.

Received for publication, June 27, 2005 , and in revised form, July 8, 2005.

^* This work was supported in part by the National Science Foundation, the National Institutes of Health, and Irma T. Hirschl Trust grants (to M. H. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by a postdoctoral fellowship from the American Heart Association.

A Distinguished Young Scholar of the W. M. Keck Foundation. To whom correspondence should be addressed: Laboratory of Molecular Biophysics, The Rockefeller University, 1230 York Ave., Box 42, New York, NY 10021. Tel.: 212-327-7221; Fax: 212-327-7222; E-mail: mwerner{at}portugal.rockefeller.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?