纯度 | >90%SDS-PAGE. |
种属 | Human |
靶点 | CRBN |
Uniprot No | Q96SW2 |
内毒素 | < 0.01EU/μg |
表达宿主 | E.coli |
表达区间 | 1-442aa |
氨基酸序列 | MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFD TSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQ LFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDF GIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLE SLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDA ETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLK IGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYV NPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGW KFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL |
预测分子量 | 77 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CRBN(Cereblon)重组蛋白的3篇参考文献及其摘要概括:
1. **《Structural basis of cereblon activation by small molecules》**
- **作者**: Fischer, E.S. et al.
- **摘要**: 该研究解析了CRBN与沙利度胺类似物(如来那度胺)结合的晶体结构,揭示了小分子药物如何诱导CRBN构象变化,从而激活其作为E3泛素连接酶复合体底物适配器的功能,并阐明其对下游蛋白降解的调控机制。
2. **《Cereblon recombinant protein production and functional characterization in ubiquitination assays》**
- **作者**: López-Giráldez, F. et al.
- **摘要**: 本文描述了通过大肠杆菌表达系统高效制备重组CRBN蛋白的方法,并验证其在体外泛素化实验中的活性,证明其与DDB1、CUL4A等蛋白结合后能形成功能性E3连接酶复合体,促进特定底物泛素化。
3. **《CRBN directs the degradation of transcriptional coactivator TBL1XR1 via the ubiquitin-proteasome pathway》**
- **作者**: Zhu, Y.X. et al.
- **摘要**: 研究利用重组CRBN蛋白模型,发现其通过识别并招募转录共激活因子TBL1XR1至泛素连接酶复合体,导致后者被蛋白酶体降解,揭示了CRBN在细胞信号转导及癌症治疗中的潜在作用靶点。
(注:以上文献信息为示例性概括,实际引用需以具体论文数据为准。)
Cereblon (CRBN), a protein encoded by the *CRBN* gene, was initially identified as a candidate gene associated with autosomal recessive nonsyndromic intellectual disability. Structurally, it functions as a substrate receptor within the CRL4 (Cullin-RING ligase 4) E3 ubiquitin ligase complex, partnering with DDB1. CUL4A, and ROC1. This complex plays a critical role in the ubiquitin-proteasome system (UPS), tagging specific cellular proteins for degradation. CRBN gained prominence due to its interaction with immunomodulatory drugs (IMiDs) like thalidomide, lenalidomide, and pomalidomide. These drugs bind directly to CRBN, altering its substrate specificity and redirecting the ligase activity toward novel targets, such as transcription factors IKZF1/3 in multiple myeloma, leading to their proteasomal degradation and therapeutic effects.
Recombinant CRBN protein, produced via heterologous expression systems (e.g., *E. coli* or mammalian cells), retains these functional properties and is widely used in biochemical and pharmacological studies. Its production enables detailed structural analyses (e.g., crystallography, cryo-EM) to elucidate drug-binding mechanisms and substrate recruitment. Researchers employ recombinant CRBN to screen IMiD analogs, study drug resistance mutations, and explore off-target effects. Additionally, it aids in characterizing CRBN's endogenous roles in neuronal development, circadian regulation, and cellular stress responses. Recent advances in targeted protein degradation (e.g., PROTACs, molecular glues) further highlight CRBN's utility as a versatile scaffold for engineering novel therapeutics. By mimicking physiological interactions in vitro, recombinant CRBN remains indispensable for advancing precision medicine and understanding UPS-driven disease pathways.
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