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

被引:0
作者
Bulatova, Leisan [1 ]
Savenkova, Daria [1 ]
Nurgalieva, Alsina [1 ]
Reshetnikova, Daria [1 ]
Timonina, Arina [1 ]
Skripova, Vera [1 ]
Bogdanov, Mikhail [1 ,2 ]
Kiyamova, Ramziya [1 ]
机构
[1] Kazan Fed Univ, Inst Fundamental Med & Biol, Res Lab Biomarker, Kazan, Russia
[2] Univ Texas Hlth Sci Ctr, McGovern Med Sch, Dept Biochem & Mol Biol, Houston, TX 77030 USA
基金
俄罗斯科学基金会;
关键词
NaPi2b; MX35; antigen; topology; ECD; monoclonal antibody; ovarian cancer; PHOSPHATE TRANSPORTER NAPI2B; ANTIBODY-DRUG CONJUGATE; MONOCLONAL-ANTIBODIES; COTRANSPORTER; EPITOPE; PREDICTION; INSERTION; ANTIGEN; BINDING; DOMAIN;
D O I
10.3389/fmolb.2022.895911
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 in silico, 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.
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页数:11
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