Crystal structure of Apaf-1 caspase recruitment domain: an alpha-helical Greek key fold for apoptotic signaling

Vaughn, D. E., Rodriguez, J., Lazebnik, Y., Joshua-Tor, L. (1999) Crystal structure of Apaf-1 caspase recruitment domain: an alpha-helical Greek key fold for apoptotic signaling. Journal of Molecular Biology, 293 (3). pp. 439-447. ISSN 0022-2836 (Public Dataset)

URL: http://www.ncbi.nlm.nih.gov/pubmed/10543941
DOI: 10.1006/jmbi.1999.3177

Abstract

The caspase recruitment domain (CARD) of Apaf-1 binds to the CARD of caspase-9 to trigger a proteolytic cascade that leads to apoptotic cell death. We report the crystal structure of the Apaf-1 CARD at 1. 3 A resolution, solved in a two-element multiwavelength anomalous dispersion (MAD) X-ray diffraction experiment. This CARD adopts a six-helix bundle fold with Greek key topology surrounding an extensive hydrophobic core. This fold, which we call the "death fold", is found in other domains that mediate interactions in apoptotic signaling despite very low sequence identity. From a structure-based alignment, we identify conserved patterns that characterize the death fold and its subclasses. Like the Ig-fold, it provides a rigid structural scaffold upon which diverse recognition surfaces are assembled.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Motifs Amino Acid Sequence Apoptosis Apoptotic Protease-Activating Factor 1 Binding Sites Caspase 9 Caspases Conserved Sequence Crystallization Crystallography, X-Ray Humans Hydrogen Bonding Immunoglobulins Models, Molecular Molecular Sequence Data Protein Folding Protein Structure, Secondary Proteins Recombinant Fusion Proteins Signal Transduction
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein structure rendering
CSHL Authors:
Communities: CSHL labs > Joshua-Tor lab
CSHL labs > Labeznik lab
Depositing User: Matt Covey
Date: 1999
Date Deposited: 12 Dec 2012 17:30
Last Modified: 06 Sep 2017 14:13
Related URLs:
Dataset ID:
URI: http://repository.cshl.edu/id/eprint/26393

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