Molecular basis of the spectral expression of CIAS1 mutations associated with phagocytic cell-mediated autoinflammatory disorders CINCA/NOMID, MWS, and FCU.

NALP proteins are recently identified members of the CATERPILLER (CARD, transcription enhancer, R(purine)-binding, pyrin, lots of LRR) family of proteins, thought to function in apoptotic and inflammatory signaling pathways. Mutations in the CIAS1 gene, which encodes a member of the NALP (NACHT-, LRR-, and PYD-containing proteins) family, the cryopyrin/NALP3/PYPAF1 protein, expressed primarily in phagocytic cells, were recently found to be associated with a spectrum of autoinflammatory disorders. These include chronic infantile neurologic cutaneous and articular (CINCA) syndrome (also known as neonatal-onset multisystem inflammatory disease [NOMID]), Muckle-Wells syndrome (MWS), and familial cold urticaria (FCU). We describe herein 7 new mutations in 13 unrelated patients with CINCA syndrome and identify mutational hotspots in CIAS1 on the basis of all mutations described to date. We also provide evidence of genotype/phenotype correlations. A 3-dimensional model of the nucleotide-binding domain (NBD) of cryopyrin suggested that this molecule is structurally and functionally similar to members of the AAA+ protein family of ATPases. According to this model, most of the mutations known to affect residues of the NBD are clustered on one side of this domain in a region predicted to participate in intermolecular contacts, suggesting that this model is likely to be biologically relevant and that defects in nucleotide binding, nucleotide hydrolysis, or protein oligomerization may lead to the functional dysregulation of cryopyrin in the MWS, FCU, and CINCA/NOMID disorders.

[1]  J. Harney,et al.  The Iodothyronine Selenodeiodinases Are Thioredoxin-fold Family Proteins Containing a Glycoside Hydrolase Clan GH-A-like Structure* , 2003, Journal of Biological Chemistry.

[2]  M. Gahr,et al.  Two German CINCA (NOMID) patients with different clinical severity and response to anti‐inflammatory treatment , 2003, European journal of haematology.

[3]  Isabelle Callebaut,et al.  Non‐intertwined binary patterns of hydrophobic/nonhydrophobic amino acids are considerably better markers of regular secondary structures than nonconstrained patterns , 2003, Proteins.

[4]  P. Berbis,et al.  CIAS1 Mutation in a Patient with Overlap between Muckle-Wells and Chronic Infantile Neurological Cutaneous and Articular Syndromes , 2003, Dermatology.

[5]  F. Martinon,et al.  NALPs: a novel protein family involved in inflammation , 2003, Nature Reviews Molecular Cell Biology.

[6]  S. Gregory,et al.  Fine structure mapping of CIAS1: identification of an ancestral haplotype and a common FCAS mutation, L353P , 2003, Human Genetics.

[7]  E. Remmers,et al.  De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. , 2002, Arthritis and rheumatism.

[8]  J. Ting,et al.  Cutting Edge: CATERPILLER: A Large Family of Mammalian Genes Containing CARD, Pyrin, Nucleotide-Binding, and Leucine-Rich Repeat Domains1 , 2002, The Journal of Immunology.

[9]  G. Hitman,et al.  Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis. , 2002, Arthritis and rheumatism.

[10]  F. Martinon,et al.  The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. , 2002, Molecular cell.

[11]  A. Fischer,et al.  Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes. , 2002, American journal of human genetics.

[12]  M. Schaller,et al.  Fire and ICE: the role of pyrin domain-containing proteins in inflammation and apoptosis. , 2002, Clinical and experimental rheumatology.

[13]  S. Srinivasula,et al.  The PYRIN-CARD Protein ASC Is an Activating Adaptor for Caspase-1* , 2002, The Journal of Biological Chemistry.

[14]  D. Scott,et al.  New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes. , 2002, American journal of human genetics.

[15]  D. Philpott,et al.  Intracellular vs extracellular recognition of pathogens--common concepts in mammals and flies. , 2002, Trends in microbiology.

[16]  J. Bertin,et al.  PYPAF1, a PYRIN-containing Apaf1-like Protein That Assembles with ASC and Regulates Activation of NF-κB* , 2002, The Journal of Biological Chemistry.

[17]  Xuejun Jiang,et al.  Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation. , 2002, Molecular cell.

[18]  R. Kolodner,et al.  Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle–Wells syndrome , 2001, Nature Genetics.

[19]  T L Blundell,et al.  FUGUE: sequence-structure homology recognition using environment-specific substitution tables and structure-dependent gap penalties. , 2001, Journal of molecular biology.

[20]  F. Martinon,et al.  The pyrin domain: a possible member of the death domain-fold family implicated in apoptosis and inflammation , 2001, Current Biology.

[21]  N. Kunishima,et al.  Crystal structure of the Holliday junction migration motor protein RuvB from Thermus thermophilus HB8. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[22]  M van Heel,et al.  Structure of the AAA ATPase p97. , 2000, Molecular cell.

[23]  A. Fayyazuddin,et al.  Molecular Organization of a Zinc Binding N-Terminal Modulatory Domain in a NMDA Receptor Subunit , 2000, Neuron.

[24]  P. Lucas,et al.  An Induced Proximity Model for NF-κB Activation in the Nod1/RICK and RIP Signaling Pathways , 2000 .

[25]  J M Berger,et al.  Structure and function of Cdc6/Cdc18: implications for origin recognition and checkpoint control. , 2000, Molecular cell.

[26]  D. Bazett-Jones,et al.  Mitotic Transcription Repression in Vivo in the Absence of Nucleosomal Chromatin Condensation , 2000, The Journal of cell biology.

[27]  M. Sternberg,et al.  Enhanced genome annotation using structural profiles in the program 3D-PSSM. , 2000, Journal of molecular biology.

[28]  L Rychlewski,et al.  ATP‐activated oligomerization as a mechanism for apoptosis regulation: Fold and mechanism prediction for CED‐4 , 2000, Proteins.

[29]  E. Koonin,et al.  The NACHT family - a new group of predicted NTPases implicated in apoptosis and MHC transcription activation. , 2000, Trends in biochemical sciences.

[30]  E. Koonin,et al.  The ATP-cone: an evolutionarily mobile, ATP-binding regulatory domain. , 2000, Journal of molecular microbiology and biotechnology.

[31]  D T Jones,et al.  Protein secondary structure prediction based on position-specific scoring matrices. , 1999, Journal of molecular biology.

[32]  E. Koonin,et al.  The domains of death: evolution of the apoptosis machinery. , 1999, Trends in biochemical sciences.

[33]  E V Koonin,et al.  AAA+: A class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes. , 1999, Genome research.

[34]  A. Brünger,et al.  Structure of the ATP-dependent oligomerization domain of N-ethylmaleimide sensitive factor complexed with ATP , 1998, Nature Structural Biology.

[35]  W. Weis,et al.  Crystal Structure of the Hexamerization Domain of N-ethylmaleimide–Sensitive Fusion Protein , 1998, Cell.

[36]  Jonathan D. G. Jones,et al.  The NB-ARC domain: a novel signalling motif shared by plant resistance gene products and regulators of cell death in animals , 1998, Current Biology.

[37]  M. Latterich,et al.  The AAA team: related ATPases with diverse functions. , 1998, Trends in cell biology.

[38]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[39]  G. Labesse,et al.  Deciphering protein sequence information through hydrophobic cluster analysis (HCA): current status and perspectives , 1997, Cellular and Molecular Life Sciences CMLS.

[40]  M. Karplus,et al.  Evaluation of comparative protein modeling by MODELLER , 1995, Proteins.

[41]  B. Rost,et al.  Combining evolutionary information and neural networks to predict protein secondary structure , 1994, Proteins.

[42]  B. Henrissat,et al.  Detection of secondary structure elements in proteins by hydrophobic cluster analysis. , 1992, Protein engineering.

[43]  J. Mornon,et al.  Hydrophobic cluster analysis: An efficient new way to compare and analyse amino acid sequences , 1987, FEBS letters.

[44]  N. Bizzaro,et al.  Autoantibody detection in scleroderma patients. Diagnostic and analytical performances of a new coupled particle light scattering immunoassay. , 2002, Clinical and experimental rheumatology.

[45]  R. Vale.  Mini-Review AAA Proteins: Lords of the Ring , 2000 .

[46]  P. Lucas,et al.  An Induced Proximity Model for NF- κ B Activation in the Nod1/RICK and RIP Signaling Pathways , 2000 .

[47]  N. Guex,et al.  SWISS‐MODEL and the Swiss‐Pdb Viewer: An environment for comparative protein modeling , 1997, Electrophoresis.

[48]  C. Griscelli,et al.  A chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome. A specific entity analysed in 30 patients. , 1987, Scandinavian journal of rheumatology. Supplement.