Blau syndrome polymorphisms in NOD2 identify nucleotide hydrolysis and helical domain 1 as signalling regulators

Autor: Joseph P. Boyle, Tom P. Monie, Rhiannon Parkhouse
Přispěvatelé: Apollo - University of Cambridge Repository
Rok vydání: 2014
Předmět:
Models
Molecular
NACHT
Nod2 Signaling Adaptor Protein
Nucleotide oligomerisation domain containing 2
NACHT
found in NAIP
CIITA
HET-E and TP-1
Biochemistry
Protein Structure
Secondary
Nucleotide-binding
leucine-rich repeat containing receptor
Structural Biology
ATP hydrolysis
Nod1 Signaling Adaptor Protein
NOD2
NOD1
Nucleotide
Receptor
NF-κB
nuclear factor kappa B
Innate immunity
Genetics
chemistry.chemical_classification
Synovitis
Hydrolysis
NF-kappa B
CAPS
cryopyrin-associated periodic syndromes
SNP
single nucleotide polymorphism
Phenotype
Protein Transport
HD
helical domain
EOS
early onset sarcoidosis
BS
Blau syndrome
Signal Transduction
Sarcoidosis
Molecular Sequence Data
Biophysics
Single-nucleotide polymorphism
Biology
Polymorphism
Single Nucleotide
Article
Uveitis
medicine
Humans
Genetic Predisposition to Disease
Amino Acid Sequence
RIP2
receptor interacting protein 2
NLR
nucleotide-binding
leucine-rich repeat containing receptor
Molecular Biology
Blau syndrome
Genetic Association Studies
Arthritis
Single nucleotide polymorphisms
Cell Biology
medicine.disease
Molecular biology
Cranial Nerve Diseases
digestive system diseases
Protein Structure
Tertiary
HEK293 Cells
Amino Acid Substitution
chemistry
NOD
nucleotide oligomerisation domain
Zdroj: Febs Letters
ISSN: 0014-5793
DOI: 10.1016/j.febslet.2014.07.029
Popis: Highlights • NOD2 SNPs that cause Blau syndrome cluster in two regions of the NACHT. • The ATP/Mg2+ binding pocket cluster are likely to dysregulate ATP hydrolysis. • SNPs in helical domain 1 are predicted to influence receptor autoinhibition. • Complementary mutations in NOD1 do not all result in hyperactivation.
Understanding how single nucleotide polymorphisms (SNPs) lead to disease at a molecular level provides a starting point for improved therapeutic intervention. SNPs in the innate immune receptor nucleotide oligomerisation domain 2 (NOD2) can cause the inflammatory disorders Blau Syndrome (BS) and early onset sarcoidosis (EOS) through receptor hyperactivation. Here, we show that these polymorphisms cluster into two primary locations: the ATP/Mg2+-binding site and helical domain 1. Polymorphisms in these two locations may consequently dysregulate ATP hydrolysis and NOD2 autoinhibition, respectively. Complementary mutations in NOD1 did not mirror the NOD2 phenotype, which indicates that NOD1 and NOD2 are activated and regulated by distinct methods.
Databáze: OpenAIRE
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