NMR Structure of the Apoptosis- and Inflammation-Related NALP1 Pyrin Domain

Signaling in apoptosis and inflammation is often mediated by proteins of the death domain superfamily in the Fas/FADD/Caspase-8 or the Apaf-1/Caspase-9 pathways. This superfamily currently comprises the death domain (DD), death effector domain (DED), caspase recruitment domain (CARD), and pyrin doma...

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Bibliographic Details
Published in:Structure (London) 2003-10, Vol.11 (10), p.1199-1205
Main Authors: Hiller, Sebastian, Kohl, Andreas, Fiorito, Francesco, Herrmann, Torsten, Wider, Gerhard, Tschopp, Jürg, Grütter, Markus G, Wüthrich, Kurt
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Apoptosis - physiology
Apoptosis Regulatory Proteins
Cytoskeletal Proteins
Humans
Inflammation - metabolism
Magnetic Resonance Spectroscopy
Multigene Family
Protein Structure, Tertiary
Proteins - chemistry
Proteins - metabolism
Pyrin
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Summary:Signaling in apoptosis and inflammation is often mediated by proteins of the death domain superfamily in the Fas/FADD/Caspase-8 or the Apaf-1/Caspase-9 pathways. This superfamily currently comprises the death domain (DD), death effector domain (DED), caspase recruitment domain (CARD), and pyrin domain (PYD) subfamilies. The PYD subfamily is most abundant, but three-dimensional structures are only available for the subfamilies DD, DED, and CARD, which have an antiparallel arrangement of six α helices as common fold. This paper presents the NMR structure of PYD of NALP1, a protein that is involved in the innate immune response and is a component of the inflammasome. The structure of NALP1 PYD differs from all other known death domain superfamily structures in that the third α helix is replaced by a flexibly disordered loop. This unique feature appears to relate to the molecular basis of familial Mediterranean fever (FMF), a genetic disease caused by single-point mutations.
ISSN:0969-2126
1878-4186
DOI:10.1016/j.str.2003.08.009