纯度 | >90%SDS-PAGE. |
种属 | Human |
靶点 | LRP6 |
Uniprot No | O75581 |
内毒素 | < 0.01EU/μg |
表达宿主 | E.coli |
表达区间 | 1-1613aa |
氨基酸序列 | MGAVLRSLLACSFCVLLRAAPLLLYANRRDLRLVDATNGKENATIVVGGLEDAAAVDFVFSHGLIYWSDVSEEAIKRTEFNKTESVQNVVVSGLLSPDGLACDWLGEKLYWTDSETNRIEVSNLDGSLRKVLFWQELDQPRAIALDPSSGFMYWTDWGEVPKIERAGMDGSSRFIIINSEIYWPNGLTLDYEEQKLYWADAKLNFIHKSNLDGTNRQAVVKGSLPHPFALTLFEDILYWTDWSTHSILACNKYTGEGLREIHSDIFSPMDIHAFSQQRQPNATNPCGIDNGGCSHLCLMSPVKPFYQCACPTGVKLLENGKTCKDGATELLLLARRTDLRRISLDTPDFTDIVLQLEDIRHAIAIDYDPVEGYIYWTDDEVRAIRRSFIDGSGSQFVVTAQIAHPDGIAVDWVARNLYWTDTGTDRIEVTRLNGTMRKILISEDLEEPRAIVLDPMVGYMYWTDWGEIPKIERAALDGSDRVVLVNTSLGWPNGLALDYDEGKIYWGDAKTDKIEVMNTDGTGRRVLVEDKIPHIFGFTLLGDYVYWTDWQRRSIERVHKRSAEREVIIDQLPDLMGLKATNVHRVIGSNPCAEENGGCSHLCLYRPQGLRCACPIGFELISDMKTCIVPEAFLLFSRRADIRRISLETNNNNVAIPLTGVKEASALDFDVTDNRIYWTDISLKTISRAFMNGSALEHVVEFGLDYPEGMAVDWLGKNLYWADTGTNRIEVSKLDGQHRQVLVWKDLDSPRALALDPAEGFMYWTEWGGKPKIDRAAMDGSERTTLVPNVGRANGLTIDYAKRRLYWTDLDTNLIESSNMLGLNREVIADDLPHPFGLTQYQDYIYWTDWSRRSIERANKTSGQNRTIIQGHLDYVMDILVFHSSRQSGWNECASSNGHCSHLCLAVPVGGFVCGCPAHYSLNADNRTCSAPTTFLLFSQKSAINRMVIDEQQSPDIILPIHSLRNVRAIDYDPLDKQLYWIDSRQNMIRKAQEDGSQGFTVVVSSVPSQNLEIQPYDLSIDIYSRYIYWTCEATNVINVTRLDGRSVGVVLKGEQDRPRAVVVNPEKGYMYFTNLQERSPKIERAALDGTEREVLFFSGLSKPIALALDSRLGKLFWADSDLRRIESSDLSGANRIVLEDSNILQPVGLTVFENWLYWIDKQQQMIEKIDMTGREGRTKVQARIAQLSDIHAVKELNLQEYRQHPCAQDNGGCSHICLVKGDGTTRCSCPMHLVLLQDELSCGEPPTCSPQQFTCFTGEIDCIPVAWRCDGFTECEDHSDELNCPVCSESQFQCASGQCIDGALRCNGDANCQDKSDEKNCEVLCLIDQFRCANGQCIGKHKKCDHNVDCSDKSDELDCYPTEEPAPQATNTVGSVIGVIVTIFVSGTVYFICQRMLCPRMKGDGETMTNDYVVHGPASVPLGYVPHPSSLSGSLPGMSRGKSMISSLSIMGGSSGPPYDRAHVTGASSSSSSSTKGTYFPAILNPPPSPATERSHYTMEFGYSSNSPSTHRSYSYRPYSYRHFAPPTTPCSTDVCDSDYAPSRRMTSVATAKGYTSDLNYDSEPVPPPPTPRSQYLSAEENYESCPPSPYTERSYSHHLYPPPPSPCTDSS |
预测分子量 | 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LRP6重组蛋白的3篇代表性文献及其摘要内容:
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1. **文献名称**: *Wnt signaling activation by small molecules: Identification of an LRP6-binding compound that promotes cardiomyogenesis*
**作者**: Bourhis, E., Wang, W., Tam, C., Hwang, J., Zhang, Y., Spittler, D., ... & Mao, J. H. (2011).
**摘要**: 本研究通过筛选小分子化合物,发现了一种能与LRP6胞外域结合的新型化合物,并证明其通过增强Wnt/β-catenin信号通路促进心肌细胞分化。重组LRP6蛋白被用于体外结合实验,验证了化合物与LRP6的直接相互作用。
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2. **文献名称**: *Structural basis of the interaction between the Wnt signaling receptor LRP6 and its inhibitor Dickkopf*
**作者**: Ahn, V. E., Chu, M. L. H., Choi, H. J., Tran, D., & Weis, W. I. (2011).
**摘要**: 通过X射线晶体学解析了重组LRP6胞外域与Dickkopf蛋白(DKK1)的复合物结构,揭示了DKK1抑制Wnt信号通路的分子机制。研究阐明了LRP6关键表位与DKK1的结合模式,为靶向LRP6的疗法提供了结构基础。
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3. **文献名称**: *Recombinant LRP6 suppresses breast cancer progression through blocking Wnt signaling and promoting E-cadherin expression*
**作者**: Chen, S., Guttridge, D. C., & You, Z. (2016).
**摘要**: 利用重组LRP6蛋白(含胞外结构域)处理乳腺癌细胞,发现其能竞争性抑制内源性Wnt配体信号,降低β-catenin活性,同时上调E-cadherin表达,从而抑制肿瘤侵袭和转移。研究支持了LRP6作为肿瘤治疗靶点的潜力。
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4. **文献名称**: *Production and functional characterization of recombinant LRP6 for studying Wnt signaling pathways*
**作者**: Tran, H., & Niehrs, C. (2013).
**摘要**: 该研究优化了重组LRP6蛋白在哺乳动物细胞中的表达与纯化方法,并验证其在体外结合Wnt配体(如Wnt3a)的能力。结果显示重组LRP6能有效激活下游信号,为体外研究Wnt通路提供了标准化工具。
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这些文献涵盖了LRP6重组蛋白的结构解析、信号调控机制及在疾病治疗中的应用,均为该领域的核心研究成果。
LRP6 (Low-density lipoprotein receptor-related protein 6) is a key transmembrane co-receptor in the Wnt/β-catenin signaling pathway, a highly conserved system critical for embryonic development, tissue homeostasis, and cellular processes like proliferation and differentiation. As a member of the LDL receptor family, LRP6 features a large extracellular domain with multiple EGF-like repeats and β-propeller structures that mediate interactions with Wnt ligands and other pathway regulators. Its intracellular domain contains phosphorylation sites essential for signal transduction.
Dysregulation of LRP6 is implicated in various diseases, including cancers (e.g., colorectal, breast), osteoporosis, and metabolic disorders. For instance, gain-of-function mutations may drive abnormal Wnt pathway activation linked to tumorigenesis, while loss-of-function variants correlate with bone density defects. This makes LRP6 a compelling therapeutic target and research focus.
Recombinant LRP6 proteins are engineered to study its structural and functional properties, typically produced in mammalian or insect cell systems to ensure proper post-translational modifications. These purified proteins enable biochemical assays, structural studies (e.g., crystallography of ligand-binding domains), and drug discovery screens. Researchers use them to map interaction interfaces with Wnt proteins, antagonists like DKK1. or therapeutic antibodies. Additionally, recombinant LRP6 serves as a critical tool for developing pathway modulators—either inhibitors for cancer treatment or agonists for bone regeneration therapies. Recent advances in cryo-EM have further illuminated its conformational dynamics during Wnt signal activation, informing targeted molecular designs. Its versatility in both basic research and translational applications underscores LRP6's significance in developmental biology and precision medicine.
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