RNASE7 Human

Ribonuclease 7 Human Recombinant
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Description

Antimicrobial Activity

RNASE7 exhibits broad-spectrum activity against Gram-positive and Gram-negative bacteria, fungi, and dermatophytes (Table 1). Its mechanisms include membrane permeabilization and disruption of bacterial cell wall integrity, often targeting lipopolysaccharides (LPS) or outer membrane proteins (e.g., OprI in Pseudomonas aeruginosa) .

Table 1: Antimicrobial Activity of RNASE7

PathogenEffective ConcentrationMechanismReference
Staphylococcus aureusn/aNeutralization reduces skin colonization .
Enterococcus faecium<30 nMDirect bactericidal activity
Pseudomonas aeruginosaMicromolar rangeBinds OprI, disrupts membrane integrity
Candida albicansMicromolar rangeMembrane lysis followed by RNA degradation
Trichophyton rubrumn/aInhibits fungal growth

Immunomodulatory Functions

RNASE7 bridges innate and adaptive immunity by modulating immune cell responses:

  • Plasmacytoid Dendritic Cells (pDCs): In combination with self-DNA, RNASE7 triggers robust IFNα production, which protects keratinocytes from herpes simplex virus (HSV-1) infection .

  • T-Cell Regulation: Reduces Th2 cytokine (IL-4, IL-5, IL-13) production in CD4+ T cells via GATA3 downregulation, independent of RNase activity .

  • Chemokine Induction: Stimulates keratinocytes to secrete IP-10 (CXCL10) and IFNβ, enhancing antiviral defenses .

Table 2: Immunomodulatory Effects of RNASE7

FunctionMechanismOutcomeReference
IFNα ProductionSelf-DNA/RNASE7 complex activation of pDCsAntiviral defense against HSV-1
Th2 Cytokine SuppressionReduced GATA3 activationMitigation of allergic inflammation
Chemokine SecretionIP-10 and IFNβ release by keratinocytesEnhanced antiviral response

Clinical and Therapeutic Significance

RNASE7 levels correlate with susceptibility to infections and inflammatory diseases:

  • Urinary Tract Infections (UTIs): Children with UTIs exhibit lower urinary RNASE7 concentrations compared to healthy controls. A polymorphism (rs1263872) in RNASE7 reduces bactericidal activity, increasing UTI risk .

  • Atopic Dermatitis (AD): Impaired RNASE7-mediated Th2 suppression may exacerbate AD pathology .

  • Therapeutic Potential: Recombinant RNASE7 or strategies to boost endogenous expression (e.g., insulin therapy) are under investigation for antibiotic-resistant infections .

Table 3: Clinical Relevance of RNASE7

ConditionRNASE7 RoleTherapeutic ImplicationsReference
UTIsLow levels correlate with infectionRecombinant RNASE7 or insulin therapy
S. aureus InfectionsNeutralization increases bacterial growthRNASE7-based topical treatments
ADDysregulated Th2 cytokine suppressionRNASE7 agonists for immune modulation

Research Findings and Future Directions

  • Genetic Variants: The rs1263872 polymorphism (G→C) reduces RNASE7’s bactericidal efficacy, increasing UTI susceptibility in children .

  • Mechanistic Insights: RNASE7 binds bacterial LPS and membrane proteins, bypassing ribonuclease activity for antimicrobial effects .

  • Therapeutic Challenges: Overcoming the ribonuclease inhibitor in human skin and optimizing delivery methods for clinical use remain critical hurdles .

Product Specs

Introduction
Ribonuclease 7 (RNASE7) is a member of the RNase A superfamily of ribonucleases. It was first discovered in the stratum corneum of the skin. RNASE7 exhibits potent ribonuclease activity, suggesting its contribution to the notable ribonuclease activity observed in human skin. Studies have demonstrated that RNASE7 possesses a broad spectrum of antimicrobial activity against various pathogenic microorganisms, including remarkably potent activity against specific pathogens.
Description
Recombinant human RNASE7, expressed in E. coli, is a single, non-glycosylated polypeptide chain comprising 151 amino acids (residues 29-156). It has a molecular weight of 16.9 kDa. The protein is engineered with a 23-amino acid His-tag at the N-terminus to facilitate purification using proprietary chromatographic techniques.
Physical Appearance
Sterile, colorless solution, filtered for purity.
Formulation
RNASE7 protein solution is provided at a concentration of 0.5 mg/ml in a buffer consisting of 20 mM Tris-HCl (pH 8.0), 10% glycerol, and 1 mM DTT.
Stability
For short-term storage (up to 2-4 weeks), the product can be stored at 4°C. For extended storage, it is recommended to store the product frozen at -20°C. To ensure long-term stability during frozen storage, the addition of a carrier protein like HSA or BSA (0.1%) is advised. Avoid repeated freeze-thaw cycles.
Purity
The purity of RNASE7 is determined to be greater than 90% using SDS-PAGE analysis.
Synonyms
Ribonuclease, RNase A Family, 7, Skin-Derived Antimicrobial Protein 2, RNase 7, SAP-2, EC 3.1.27.5, EC 3.1.27., EC 3.1.27, Ribonuclease 7.
Source
Escherichia Coli.
Amino Acid Sequence
MGSSHHHHHH SSGLVPRGSH MGSKPKGMTS SQWFKIQHMQ PSPQACNSAM KNINKHTKRC KDLNTFLHEP FSSVAATCQT PKIACKNGDK NCHQSHGPVS LTMCKLTSGK YPNCRYKEKR QNKSYVVACK PPQKKDSQQF HLVPVHLDRV L.

Product Science Overview

Introduction

Ribonuclease 7 (RNase 7) is a member of the Ribonuclease A superfamily, which consists of structurally similar peptides secreted by immune cells and epithelial tissues. RNase 7 is particularly notable for its potent broad-spectrum antimicrobial activity, making it a significant component of the human innate immune system .

Discovery and Source

RNase 7 was initially isolated from the stratum corneum, the outermost layer of human skin . This protein exhibited strong ribonuclease activity, contributing to the overall ribonuclease activity observed in human skin. The recombinant form of RNase 7 is typically produced in Escherichia coli (E. coli) and purified using conventional chromatography techniques .

Structure and Properties

RNase 7 is a cationic peptide, meaning it carries a positive charge, which is crucial for its interaction with negatively charged microbial membranes. The protein consists of 128 amino acids and has a molecular weight of approximately 16.9 kDa . The recombinant version often includes an N-terminal His-tag to facilitate purification and detection .

Antimicrobial Activity

One of the most remarkable features of RNase 7 is its broad-spectrum antimicrobial activity. It has been shown to be effective against a wide range of pathogenic microorganisms, including bacteria, fungi, and viruses . Notably, RNase 7 exhibits potent activity against vancomycin-resistant Enterococcus faecium, a significant concern in clinical settings due to its resistance to multiple antibiotics .

Mechanism of Action

The antimicrobial activity of RNase 7 is primarily attributed to its ability to degrade RNA within microbial cells. By cleaving RNA, RNase 7 disrupts essential cellular processes, leading to the death of the microorganism . Additionally, its cationic nature allows it to interact with and disrupt microbial membranes, further enhancing its antimicrobial efficacy .

Regulation and Expression

RNase 7 is predominantly expressed in epithelial tissues, including the skin, respiratory tract, and urinary tract . Its expression is regulated by various factors, including microbial presence and inflammatory signals. This regulation ensures that RNase 7 is produced in response to infection, providing a rapid and effective defense mechanism .

Potential Therapeutic Applications

Given its potent antimicrobial properties, RNase 7 holds promise as a novel therapeutic agent for treating infections, particularly those caused by antibiotic-resistant bacteria . Further research is needed to fully understand its potential and to develop effective delivery methods for clinical use.

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