2L6A

Three-dimensional structure of the N-terminal effector PYRIN domain of NLRP12

Summary for 2L6A

• Entry DOI: 10.2210/pdb2l6a/pdb
• NMR Information: BMRB: 17305
• Descriptor: NACHT, LRR and PYD domains-containing protein 12 (1 entity in total)
• Functional Keywords: nlrp12, pyrin, death domain, signaling protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 11721.42

Authors

Pinheiro, A.S.,Peti, W. (deposition date: 2010-11-17, release date: 2011-11-02, Last modification date: 2024-05-15)

Primary citation

Pinheiro, A.S.,Eibl, C.,Ekman-Vural, Z.,Schwarzenbacher, R.,Peti, W.
The NLRP12 pyrin domain: structure, dynamics, and functional insights.
J.Mol.Biol., 413:790-803, 2011

PubMed Abstract: The initial line of defense against infection is sustained by the innate immune system. Together, membrane-bound Toll-like receptors and cytosolic nucleotide-binding domain and leucine-rich repeat-containing receptors (NLR) play key roles in the innate immune response by detecting bacterial and viral invaders as well as endogenous stress signals. NLRs are multi-domain proteins with varying N-terminal effector domains that are responsible for regulating downstream signaling events. Here, we report the structure and dynamics of the N-terminal pyrin domain of NLRP12 (NLRP12 PYD) determined using NMR spectroscopy. NLRP12 is a non-inflammasome NLR that has been implicated in the regulation of Toll-like receptor-dependent nuclear factor-κB activation. NLRP12 PYD adopts a typical six-helical bundle death domain fold. By direct comparison with other PYD structures, we identified hydrophobic residues that are essential for the stable fold of the NLRP PYD family. In addition, we report the first in vitro confirmed non-homotypic PYD interaction between NLRP12 PYD and the pro-apoptotic protein Fas-associated factor 1 (FAF-1), which links the innate immune system to apoptotic signaling. Interestingly, all residues that participate in this protein:protein interaction are confined to the α2-α3 surface, a region of NLRP12 PYD that differs most between currently reported NLRP PYD structures. Finally, we experimentally highlight a significant role for tryptophan 45 in the interaction between NLRP12 PYD and the FAF-1 UBA domain.

PubMed: 21978668
DOI: 10.1016/j.jmb.2011.09.024

Experimental method

SOLUTION NMR