SRP54 Human
Description
Molecular Structure of SRP54
SRP54 consists of three functional domains :
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N-terminal domain (N-domain): Stabilizes the GTPase domain.
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GTPase domain (G-domain): Facilitates GTP-dependent interaction with the SRP receptor (SR). Contains conserved G motifs (G1–G5) critical for nucleotide binding .
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Methionine-rich domain (M-domain): Binds signal peptides of nascent proteins and SRP RNA .
Structural studies reveal that disease-causing mutations (e.g., Thr117del, Cys136Tyr) destabilize the GTPase core, impairing GTP binding and receptor interaction .
Functional Role in Protein Targeting
SRP54 is a core component of the signal recognition particle (SRP), a ribonucleoprotein complex comprising six proteins (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72) and 7SL RNA . Its functions include:
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Signal peptide recognition: Binds N-terminal signal sequences of nascent polypeptides .
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ER targeting: Forms a GTP-dependent complex with the SRP receptor on the ER membrane, enabling protein translocation .
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Co-translational regulation: Ensures proper localization of secretory/membrane proteins .
Key Phenotypes469:
| Feature | Prevalence (%) | Severity |
|---|---|---|
| Chronic neutropenia | 100 | ANC < 0.5 × 10⁹/L |
| Dysgranulopoiesis | 95 | Promyelocytic arrest |
| Neurodevelopmental delay | 22 | Severe cognitive impairment |
| Exocrine pancreatic insufficiency | 13 | Requires enzyme therapy |
Mechanisms of Disease:
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ER stress and autophagy: Mutations disrupt protein targeting, leading to unfolded protein response (UPR) and apoptosis via p53 activation .
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Impaired granulopoiesis: Reduced proliferation of myeloid cells due to G-CSF receptor mislocalization and signaling defects .
Research Applications of Recombinant SRP54
Recombinant human SRP54 (e.g., PRO-113 from Prospec Bio) is used in :
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Autoantibody detection: ELISA/Western blot for anti-SRP antibodies in polymyositis.
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Functional studies: Analysis of GTPase activity and signal peptide binding.
| Property | Specification |
|---|---|
| Source | Sf9 insect cells |
| Purity | >80% (SDS-PAGE) |
| Formulation | 16 mM HEPES, 320 mM NaCl, 20% glycerol |
| Stability | -20°C long-term; 4°C for short-term |
Mutation Spectrum469
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Recurrent mutations: Thr117del (in-frame deletion, 61% of cases).
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Functional impact: Reduced GTPase activity and SRP receptor binding .
Cellular Consequences46
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Apoptosis: Upregulation of pro-apoptotic genes (BAX, NOXA1).
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ER stress markers: Increased spliced XBP1, phosphorylated eIF2α, and PERK.
Therapeutic Challenges
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Poor response to granulocyte colony-stimulating factor (G-CSF) .
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No reported leukemic transformation despite long-term follow-up .
Future Directions
Product Specs
This product consists of a full-length cDNA sequence encoding the human SRP54 protein. This protein has a molecular mass of 62kDa (determined at pH 8.9) and is fused to a hexa-histidine tag for purification purposes.
The SRP54 protein is provided in a buffer solution containing 16mM HEPES (pH 8.0), 320mM NaCl, 5mM DTT, 1mM EDTA, 0.16mM GDP, and 20% glycerol.
1. This protein can bind to IgG-type human autoantibodies.
2. This protein can be used as a standard in ELISA tests, including checkerboard analysis with positive and negative serum panels, and in immunodot tests with positive and negative serum panels.
For short-term storage (2-4 weeks), the product can be stored at 4°C. For long-term storage, it should be stored frozen at -20°C. Repeated freeze-thaw cycles should be avoided.
Product Science Overview
Signal Recognition Particle 54kDa (SRP54) is a crucial component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER) . This article delves into the background, structure, function, and significance of SRP54, particularly focusing on its human recombinant form.
