PDBsum entry 2wl1

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protein ligands links
Signaling protein PDB id
Jmol PyMol
Protein chain
191 a.a. *
SCN ×2
EDO ×3
Waters ×162
* Residue conservation analysis
PDB id:
Name: Signaling protein
Title: Pyrin pryspry domain
Structure: Pyrin. Chain: a. Fragment: pryspry, residues 586-776. Synonym: marenostrin. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.
1.35Å     R-factor:   0.194     R-free:   0.219
Authors: C.Weinert,P.R.Mittl,M.G.Gruetter
Key ref:
C.Weinert et al. (2009). The crystal structure of human pyrin b30.2 domain: implications for mutations associated with familial Mediterranean fever. J Mol Biol, 394, 226-236. PubMed id: 19729025 DOI: 10.1016/j.jmb.2009.08.059
19-Jun-09     Release date:   20-Oct-09    
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Protein chain
Pfam   ArchSchema ?
O15553  (MEFV_HUMAN) -  Pyrin
781 a.a.
191 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain


DOI no: 10.1016/j.jmb.2009.08.059 J Mol Biol 394:226-236 (2009)
PubMed id: 19729025  
The crystal structure of human pyrin b30.2 domain: implications for mutations associated with familial Mediterranean fever.
C.Weinert, C.Grütter, H.Roschitzki-Voser, P.R.Mittl, M.G.Grütter.
The inherited autoinflammatory syndrome familial Mediterranean fever (FMF) is characterized by recurrent episodes of fever, which are independent of any bacterial or viral infections. This disease is associated with point mutations in the mefv gene product pyrin. Although the precise molecular functions of pyrin are unknown, it seems to be involved in the maturation and secretion of interleukin-1beta. Approximately two thirds of all FMF-associated mutations cluster in the C-terminal B30.2 domain of pyrin. To investigate the molecular consequences of FMF-associated mutations, we determined the crystal structure of the pyrin B30.2 domain at 1.35-A resolution. The comparison with other B30.2/ligand complex structures revealed a shallow cavity, which seems to be involved in binding the pyrin ligand. The bottom of this cavity is covered mainly with hydrophobic amino acids, suggesting that pyrin recognizes its ligand by hydrophobic contacts and surface complementarities. FMF-associated mutations cluster around two sites on the B30.2 surface. Approximately two thirds, including those mutations with the most severe disease outcomes, are observed in the vicinity of the predicted peptide binding site, suggesting that they will have a direct impact on ligand binding. A second mutational hot spot was observed on the opposite side of the B30.2 domain in the neighbourhood of its artificial N-terminus. Although most FMF-associated mutations are solvent exposed, several will modify the main-chain conformation of loops. The experimental crystal structure of the pyrin B30.2 domain serves as a basis for an accurate modelling of these mutations.
  Selected figure(s)  
Figure 1.
Fig. 1. (a) Ribbon diagram of the pyrin B30.2 domain showing the Pry and Spry subdomains in red and green, respectively. This standard orientation shows the Pry subdomain on the left and with the central cavity in front. Loops that are most likely involved in the recognition of the binding partner are indicated in red letters. (b) Topology diagram of the B30.2 fold.
Figure 4.
Fig. 4. Electrostatic surfaces of B30.2 domains from (a) pyrin, (b) sRFPL1, and (c) Trim21. The electrostatic potentials were contoured red and blue at − 4 and +4, respectively. The bound ethylene glycol molecule in pyrin B30.2 and the bound peptides in sRFPL1 and Trim21 are indicated. Molecules are all shown in the standard orientation as defined in Fig. 1a.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2009, 394, 226-236) copyright 2009.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20671522 C.Henderson, and R.Goldbach-Mansky (2010).
Monogenic autoinflammatory diseases: new insights into clinical aspects and pathogenesis.
  Curr Opin Rheumatol, 22, 567-578.  
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