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 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 alpha 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 alpha 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.
Hiller
Sebastian
S
Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule Zürich, CH-8093, Zürich, Switzerland.
Kohl
Andreas
A
Fiorito
Francesco
F
Herrmann
Torsten
T
Wider
Gerhard
G
Tschopp
Jürg
J
Grütter
Markus G
MG
Wüthrich
Kurt
K
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D003598:Cytoskeletal Proteins; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D005810:Multigene Family; D000070576:NLR Proteins; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D000071198:Pyrin
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000070576:NLR Proteins; C427903:NLRP1 protein, human; D011506:Proteins; D000071198:Pyrin