纯度 | >90%SDS-PAGE. |
种属 | Human |
靶点 | GSDMD |
Uniprot No | P57764 |
内毒素 | < 0.01EU/μg |
表达宿主 | E.coli |
表达区间 | 1-484aa |
氨基酸序列 | MGSAFERVVRRVVQELDHGGEFIPVTSLQSSTGFQPYCLVVRKPSSSWFW KPRYKCVNLSIKDILEPDAAEPDVQRGRSFHFYDAMDGQIQGSVELAAPG QAKIAGGAAVSDSSSTSMNVYSLSVDPNTWQTLLHERHLRQPEHKVLQQL RSRGDNVYVVTEVLQTQKEVEVTRTHKREGSGRFSLPGATCLQGEGQGHL SQKKTVTIPSGSTLAFRVAQLVIDSDLDVLLFPDKKQRTFQPPATGHKRS TSEGAWPQLPSGLSMMRCLHNFLTDGVPAEGAFTEDFQGLRAEVETISKE LELLDRELCQLLLEGLEGVLRDQLALRALEEALEQGQSLGPVEPLDGPAG AVLECLVLSSGMLVPELAIPVVYLLGALTMLSETQHKLLAEALESQTLLG PLELVGSLLEQSAPWQERSTMSLPPGLLGNSWGEGAPAWVLLDECGLELG EDTPHVCWEPQAQGRMCALYASLALLSGLSQEPH |
预测分子量 | 79 kDa |
蛋白标签 | His tag N-Terminus |
缓冲液 | PBS, pH7.4, containing 0.01% SKL, 1mM DTT, 5% Trehalose and Proclin300. |
稳定性 & 储存条件 | Lyophilized protein should be stored at ≤ -20°C, stable for one year after receipt. Reconstituted protein solution can be stored at 2-8°C for 2-7 days. Aliquots of reconstituted samples are stable at ≤ -20°C for 3 months. |
复溶 | Always centrifuge tubes before opening.Do not mix by vortex or pipetting. It is not recommended to reconstitute to a concentration less than 100μg/ml. Dissolve the lyophilized protein in distilled water. Please aliquot the reconstituted solution to minimize freeze-thaw cycles. |
以下是关于GSDMD重组蛋白的3篇关键参考文献及其摘要概括:
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1. **文献名称**:*Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death*
**作者**:Shi J. et al. (Nature, 2015)
**摘要**:该研究首次阐明GSDMD是炎性caspase(如caspase-1/4/5/11)的底物,其被切割后释放N端结构域,介导细胞焦亡。重组GSDMD蛋白实验证明其N端可在细胞膜上成孔,导致细胞肿胀破裂和IL-1β释放。
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2. **文献名称**:*Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling*
**作者**:Kayagaki N. et al. (Nature, 2015)
**摘要**:研究发现caspase-11通过切割GSDMD激活非经典炎症小体通路,重组GSDMD的N端结构域被证明足以诱导细胞焦亡,并触发体内脓毒症模型的炎症反应,揭示了GSDMD重组蛋白在先天免疫中的关键作用。
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3. **文献名称**:*Structure insight into GSDMD reveals the basis of GSDMD auto-inhibition in cell pyroptosis*
**作者**:Liu X. et al. (Science, 2017)
**摘要**:通过重组GSDMD蛋白的晶体结构解析,揭示了其C端结构域如何抑制N端的成孔活性,而caspase切割解除自抑制。该研究为设计靶向GSDMD的炎症性疾病药物提供了结构基础。
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4. **文献名称**:*GSDMD membrane pore formation constitutes a mechanism of pyroptotic cell death*
**作者**:Deng W. et al. (Cell Reports, 2018)
**摘要**:利用重组GSDMD蛋白的脂质体实验,直接验证其N端可在细胞膜上形成孔道,导致离子流动和细胞焦亡。研究还证明GSDMD成孔活性在体内炎症反应和败血症中起关键作用。
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以上文献聚焦GSDMD重组蛋白在细胞焦亡机制、结构解析及疾病模型中的应用,均为该领域的里程碑研究。
Gasdermin D (GSDMD) is a pivotal executor of pyroptosis, a lytic form of programmed cell death associated with inflammatory responses. As a member of the gasdermin protein family, GSDMD contains two functional domains: an N-terminal pore-forming domain and a C-terminal autoinhibitory domain. Under physiological conditions, these domains remain bound, maintaining GSDMD in an inactive state. Upon cellular stress or pathogen detection, inflammatory caspases (e.g., caspase-1. -4. -5. or -11) cleave GSDMD at a specific site within the linker region, releasing the N-terminal fragment. This active fragment oligomerizes and inserts into cell membranes, forming pores that disrupt ion gradients, induce cell swelling, and ultimately lead to membrane rupture. This process facilitates the release of pro-inflammatory cytokines (e.g., IL-1β, IL-18) and danger-associated molecular patterns (DAMPs), amplifying immune signaling.
Recombinant GSDMD proteins are widely used to study pyroptosis mechanisms and screen therapeutic agents targeting inflammatory diseases. Engineered via heterologous expression systems (e.g., E. coli or mammalian cells), these proteins retain key functional features of native GSDMD, including caspase cleavage sensitivity and pore-forming activity. Researchers employ recombinant GSDMD to investigate structural determinants of pore assembly, evaluate caspase specificity, and develop inhibitors to mitigate excessive inflammation in conditions like sepsis, arthritis, or inflammatory bowel disease. Mutant variants (e.g., cleavage-resistant or pore-defective forms) are also generated to dissect functional domains or create dominant-negative tools. Purification tags (e.g., His-tag) and validation methods (e.g., SDS-PAGE, liposome leakage assays) ensure protein quality and bioactivity. Its role in bridging innate immunity and cell death makes GSDMD a critical target for understanding infection responses, autoimmune disorders, and cancer immunotherapy strategies.
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