LY86 Human

What is the LY86 gene and its protein product?

LY86, also known as MD-1, is a protein-coding gene involved in the regulation of immune responses. The protein functions as a co-receptor for TLR4 and plays a crucial role in the recognition of bacterial lipopolysaccharides (LPS), triggering the activation of the immune system. As part of the TLR4 signaling complex, LY86 contributes to the initiation of inflammatory responses by promoting the production of pro-inflammatory cytokines and type I interferons, highlighting its significance in the innate immune system's ability to detect and respond to bacterial infections . The gene has been implicated in various pathways including immune system processes, Rap1 signal pathway, B cell receptor signal pathway, and PPAR signal pathway .

What are the structural characteristics of the LY86 protein?

The human LY86 protein has a calculated molecular weight of 23.1 kDa. The expression domain of recombinant Human LY86 consists of amino acids 21-162 . The protein is involved in multiple cellular processes including apoptosis, inflammatory responses, humoral immune responses, and signal transduction . The LY86 coding gene can be modified with N-terminal 10xHis tag and C-terminal Myc tag to facilitate detection and purification in experimental settings .

Where is the LY86 gene located in the human genome?

The LY86 gene is located at cytogenetic location 6p25.1 on the human genome . Its genomic details include:

• HGNC symbol: LY86

• Aliases: MD1, MD-1, MMD-1, dJ80N2.1

• OMIM: 605241

• Ensembl: ENSG00000112799

• UniProt/Swiss-Prot: LY86_HUMAN

• Entrez Gene: 9450

• UniGene: 653138

How is LY86 implicated in obesity research?

LY86 has been identified as a gene that is consistently altered in obese individuals. Studies have shown that the gene is highly methylated in obese individuals compared to lean controls. This association has been consistently observed in progressively larger study groups, indicating that the methylation of LY86 is significantly important in obesity . The alteration in LY86 appears to be an epigenetic response to environmental factors such as high-fat foods and chemical exposures, demonstrating how food and environment can chemically alter gene function .

What is the relationship between LY86 and inflammatory conditions?

High methylation of LY86 has been associated with increased inflammation, which is a risk factor for various diseases including heart disease and cancer. The same methylation patterns are also linked to insulin resistance, a cause of diabetes . LY86's role in inflammation is further supported by its function in the TLR4 signaling complex, where it helps initiate inflammatory responses by promoting the production of pro-inflammatory cytokines . These findings suggest that LY86 may contribute to a range of inflammatory conditions beyond just obesity.

What is the significance of LY86 in carotid atherosclerosis?

LY86 has been identified as one of the core genes with higher expression in carotid atherosclerosis. Research indicates that the higher the expression of LY86, the worse the prognosis for patients with carotid atherosclerosis . Comparative toxicogenomics database (CTD) analysis has shown that LY86 is associated with pneumonia, inflammation, necrosis, and drug hypersensitivity, which may explain its role in various pathological conditions including atherosclerosis . This makes LY86 a potential biomarker for carotid atherosclerosis and possibly other cardiovascular diseases.

What experimental approaches are used to study LY86 methylation patterns?

Researchers studying LY86 methylation typically employ genome-wide association studies comparing DNA from individuals with different phenotypes (e.g., obese vs. lean). In one notable study, scientists progressively examined larger groups to confirm that LY86 was consistently and highly methylated in obese individuals . The methodology involves:

• DNA extraction from study subjects

• Methylation analysis using techniques such as bisulfite sequencing or methylation-specific PCR

• Statistical comparison of methylation patterns between study groups

• Validation in independent cohorts to confirm findings

How can protein-protein interaction networks be used to study LY86 function?

Protein-protein interaction (PPI) networks provide valuable insights into the functional relationships of LY86 with other proteins. Researchers can construct these networks using databases like STRING (Search Tool for the Retrieval of Interacting Genes) . The methodology typically involves:

• Inputting gene lists into the STRING database with a confidence score >0.4

• Visualizing the PPI network using software like Cytoscape

• Analyzing the network to identify core gene clusters using algorithms such as Maximal Clique Centrality (MCC) and Maximum Neighborhood Component (MNC)

• Validating key interactions using experimental approaches

Through this approach, researchers have identified that LY86 interacts with other core genes including TYROBP, FCER1G, IL10RA, ITGB2, LCP2, FCGR2B, CD86, and CCR1 in the context of carotid atherosclerosis .

What is known about LY86 polymorphisms and their relevance to human longevity?

LY86 has been implicated in human longevity through genome-wide association studies. Research comparing 801 centenarians and 914 healthy controls identified significant associations between specific LY86 polymorphisms and longevity . The SNP rs3804474 in LY86 was among 281 SNPs found to discriminate between centenarians and controls, suggesting its potential role in promoting longer lifespan . This indicates that genetic variations in LY86 may influence not only disease processes but also healthy aging and longevity.

How is LY86 expression regulated at the post-transcriptional level?

LY86 expression is regulated by various microRNAs (miRNAs), which are small non-coding RNA molecules that bind to complementary sequences on target mRNAs to regulate gene expression post-transcriptionally. While specific miRNAs regulating LY86 were not explicitly listed in the search results, researchers use platforms like TargetScan to predict regulatory miRNAs for genes of interest . Understanding these regulatory mechanisms is crucial for developing potential therapeutic interventions targeting LY86 expression in various disease contexts.

How can contradictory findings in LY86 studies be reconciled across different experimental systems?

Researchers encountering contradictory findings in LY86 studies should consider:

• Tissue-specific effects: LY86 may function differently in various tissues

• Species differences: Human LY86 may behave differently than in animal models

• Experimental conditions: Variations in in vitro vs. in vivo settings can affect results

• Genetic background: Different study populations may have distinct genetic modifiers

• Environmental factors: Exposures to different environmental factors may explain divergent results

• Methodological differences: Variations in sample collection, processing, and analysis techniques

Rigorous experimental design with appropriate controls, replication in independent cohorts, and meta-analyses across multiple studies can help reconcile contradictory findings .

What are the emerging therapeutic opportunities targeting LY86 in inflammatory diseases?

While the search results don't explicitly mention therapeutic interventions targeting LY86, its involvement in obesity, inflammation, and atherosclerosis suggests several potential approaches:

• Epigenetic therapies: Targeting the methylation status of LY86 could potentially modify its expression in obesity-related conditions

• Anti-inflammatory approaches: Modulating LY86's role in TLR4 signaling might reduce inflammatory responses

• miRNA-based therapies: Developing miRNA mimics or inhibitors that regulate LY86 expression could offer precision medicine approaches

• Biomarker development: LY86 expression levels could serve as biomarkers for disease progression or treatment response in atherosclerosis

Further research is needed to validate these approaches in preclinical models before clinical translation.

What are the optimal expression systems for recombinant LY86 protein production?

The E. coli expression system has been successfully used for recombinant human LY86 protein production. The expression domain typically includes amino acids 21-162 of the human protein. To facilitate detection and purification, the LY86 coding gene can be modified to include an N-terminal 10xHis tag and C-terminal Myc tag . This approach simplifies downstream processing and allows for more efficient experimental use of the recombinant protein in functional studies, protein-protein interaction analyses, and structural investigations.

What bioinformatic resources are available for LY86 research?

Several bioinformatic resources are available for researchers studying LY86:

These resources enable comprehensive analysis of LY86 from genomic, transcriptomic, proteomic, and systems biology perspectives .