Dataset Information

Insights into the Molecular Mechanisms Underlying Mammalian P2X7 Receptor Functions and Contributions in Diseases, Revealed by Structural Modeling and Single Nucleotide Polymorphisms.

ABSTRACT: The mammalian P2X7 receptors (P2X7Rs), a member of the ionotropic P2X receptor family with distinctive functional properties, play an important part in mediating extracellular ATP signaling in health and disease. A clear delineation of the molecular mechanisms underlying the key receptor properties, such as ATP-binding, ion permeation, and large pore formation of the mammalian P2X7Rs, is still lacking, but such knowledge is crucial for a better understanding of their physiological functions and contributions in diseases and for development of therapeutics. The recent breakthroughs in determining the atomic structures of the zebrafish P2X4.1R in the closed and ATP-bound open states have provided the long-awaited structural information. The human P2RX7 gene is abundant with non-synonymous single nucleotide polymorphisms (NS-SNPs), which generate a repertoire of human P2X7Rs with point mutations. Characterizations of the NS-SNPs identified in patients of various disease conditions and the resulting mutations have informed previously unknown molecular mechanisms determining the mammalian P2X7R functions and diseases. In this review, we will discuss the new insights into such mechanisms provided by structural modeling and recent functional and genetic linkage studies of NS-SNPs.

SUBMITTER: Jiang LH

PROVIDER: S-EPMC3646254 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Insights into the Molecular Mechanisms Underlying Mammalian P2X7 Receptor Functions and Contributions in Diseases, Revealed by Structural Modeling and Single Nucleotide Polymorphisms.

Jiang Lin-Hua LH Baldwin Jocelyn M JM Roger Sebastien S Baldwin Stephen A SA

Frontiers in pharmacology 20130507

The mammalian P2X7 receptors (P2X7Rs), a member of the ionotropic P2X receptor family with distinctive functional properties, play an important part in mediating extracellular ATP signaling in health and disease. A clear delineation of the molecular mechanisms underlying the key receptor properties, such as ATP-binding, ion permeation, and large pore formation of the mammalian P2X7Rs, is still lacking, but such knowledge is crucial for a better understanding of their physiological functions and ...[more]

PMID: 23675347

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Project description:BACKGROUND: Studies on the relationship between disease and genetic variations such as single nucleotide polymorphisms (SNPs) are important. Genetic variations can cause disease by influencing important biological regulation processes. Despite the needs for analyzing SNP and disease correlation, most existing databases provide information only on functional variants at specific locations on the genome, or deal with only a few genes associated with disease. There is no combined resource to widely support gene-, SNP-, and disease-related information, and to capture relationships among such data. Therefore, we developed an integrated database-pipeline system for studying SNPs and diseases. RESULTS: To implement the pipeline system for the integrated database, we first unified complicated and redundant disease terms and gene names using the Unified Medical Language System (UMLS) for classification and noun modification, and the HUGO Gene Nomenclature Committee (HGNC) and NCBI gene databases. Next, we collected and integrated representative databases for three categories of information. For genes and proteins, we examined the NCBI mRNA, UniProt, UCSC Table Track and MitoDat databases. For genetic variants we used the dbSNP, JSNP, ALFRED, and HGVbase databases. For disease, we employed OMIM, GAD, and HGMD databases. The database-pipeline system provides a disease thesaurus, including genes and SNPs associated with disease. The search results for these categories are available on the web page http://diseasome.kobic.re.kr/, and a genome browser is also available to highlight findings, as well as to permit the convenient review of potentially deleterious SNPs among genes strongly associated with specific diseases and clinical phenotypes. CONCLUSION: Our system is designed to capture the relationships between SNPs associated with disease and disease-causing genes. The integrated database-pipeline provides a list of candidate genes and SNP markers for evaluation in both epidemiological and molecular biological approaches to diseases-gene association studies. Furthermore, researchers then can decide semi-automatically the data set for association studies while considering the relationships between genetic variation and diseases. The database can also be economical for disease-association studies, as well as to facilitate an understanding of the processes which cause disease. Currently, the database contains 14,674 SNP records and 109,715 gene records associated with human diseases and it is updated at regular intervals.

Dataset Information

Insights into the Molecular Mechanisms Underlying Mammalian P2X7 Receptor Functions and Contributions in Diseases, Revealed by Structural Modeling and Single Nucleotide Polymorphisms.

Publications

Insights into the Molecular Mechanisms Underlying Mammalian P2X7 Receptor Functions and Contributions in Diseases, Revealed by Structural Modeling and Single Nucleotide Polymorphisms.

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