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PDBsum entry 2km6
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Signaling protein, protein binding
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PDB id
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2km6
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References listed in PDB file
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Key reference
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Title
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Three-Dimensional structure of the nlrp7 pyrin domain: insight into pyrin-Pyrin-Mediated effector domain signaling in innate immunity.
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Authors
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A.S.Pinheiro,
M.Proell,
C.Eibl,
R.Page,
R.Schwarzenbacher,
W.Peti.
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Ref.
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J Biol Chem, 2010,
285,
27402-27410.
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PubMed id
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Abstract
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The innate immune system provides an initial line of defense against infection.
NLR (NOD-like) receptors play a critical role in the innate immune response by
surveying the cytoplasm for traces of intracellular invaders and endogenous
stress signals. NLRs themselves are multi-domain proteins. Their N-terminal
effector domains (typically a PYRIN or CARD domain) are responsible for driving
downstream signaling and initiating the formation of inflammasomes,
multi-component complexes necessary for cytokine activation. However, the
currently available structures of NLR effector domains have not yet revealed the
mechanism of their differential modes of interaction. Here, we report the
structure and dynamics of the N-terminal pyrin domain of NLRP7 (NLRP7 PYD)
obtained by NMR spectroscopy. The NLRP7 PYD adopts a 6 alpha-helix bundle death
domain fold. A comparison of conformational and dynamics features of the NLRP7
PYD with other PYDs showed distinct differences for helix alpha3 and loop
alpha2-alpha3, which, in NLRP7, is stabilized by a strong hydrophobic cluster.
Moreover, the NLRP7 and NLRP1 PYDs have different electrostatic surfaces. This
is significant, as death domain signaling is driven by electrostatic contacts
and stabilized by hydrophobic interactions. Thus, these results provide new
insights into NLRP signaling and provide a first molecular understanding of
inflammasome formation.
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