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迈向基于拓扑结构的膜蛋白治疗性设计:在活的卵巢癌细胞中验证NaPi2b拓扑结构

Toward a Topology-Based Therapeutic Design of Membrane Proteins: Validation of NaPi2b Topology in Live Ovarian Cancer Cells.

作者信息

Bulatova Leisan, Savenkova Daria, Nurgalieva Alsina, Reshetnikova Daria, Timonina Arina, Skripova Vera, Bogdanov Mikhail, Kiyamova Ramziya

机构信息

Research Laboratory "Biomarker", Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation.

Department of Biochemistry and Molecular Biology, McGovern Medical School, the University of Texas Health Science Center, Houston, TX, United States.

出版信息

Front Mol Biosci. 2022 Jul 15;9:895911. doi: 10.3389/fmolb.2022.895911. eCollection 2022.

Abstract

NaPi2b is a sodium-dependent phosphate transporter that belongs to the SLC34 family of transporters which is mainly responsible for phosphate homeostasis in humans. Although NaPi2b is widely expressed in normal tissues, its overexpression has been demonstrated in ovarian, lung, and other cancers. A valuable set of antibodies, including L2 (20/3) and MX35, and its humanized versions react strongly with an antigen on the surface of ovarian and other carcinoma cells. Although the topology of NaPi2b was predicted , no direct experimental data are available for the orientation of NaPi2b extracellular domains in cancer cells. The presented results of antibody mapping of untagged NaPi2b in live ovarian carcinoma cells OVCAR-4 provide a platform for current and future epitope-based cancer therapies and serological diagnostics.

摘要

NaPi2b是一种钠依赖性磷酸盐转运蛋白,属于SLC34转运蛋白家族,主要负责人体的磷酸盐稳态。尽管NaPi2b在正常组织中广泛表达,但其在卵巢癌、肺癌和其他癌症中已被证明存在过表达。一组有价值的抗体,包括L2(20/3)和MX35及其人源化版本,能与卵巢癌和其他癌细胞表面的一种抗原发生强烈反应。尽管已预测了NaPi2b的拓扑结构,但尚无关于NaPi2b细胞外结构域在癌细胞中取向的直接实验数据。本文展示的在活的卵巢癌细胞OVCAR-4中对未标记的NaPi2b进行抗体定位的结果,为当前和未来基于表位的癌症治疗及血清学诊断提供了一个平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3518/9335355/daf6fa7bd7d8/fmolb-09-895911-g001.jpg

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