Analyses of the glycan structure of which Klotho recognizes

Klotho 识别的聚糖结构分析

基本信息

批准号：
21390058
负责人：
IMURA Akihiko
金额：
$ 11.32万
依托单位：
公益財団法人先端医療振興財団 (2011)Kyoto University (2009-2010)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2011
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390058/
关键词：
受容体細胞内シグナル伝達アルファークロトーグルクロン酸糖鎖レクチンクロトーレクチンファミリー電解質(リン・カルシウム)表面プラズモン共鳴(SPR)線維芽細胞増殖因子(FGF)糖鎖有機合成質量分析(MS-MS)原子間力顕微鏡(AFM)3-硫酸化グルクロン酸

项目摘要

Beta-Klotho, a type-I single-spanning membrane protein, has two tandem glycosidase-like domains and is expressed mainly in hepatocyte. The gene, beta-klotho, and alpha-Klotho belong to the Klotho family.FGF19 was identified as a lipid mediator ; which controls bile acids synthesis to regulate lipid intake. The FGF19 protein is expressed in ileum to input signal in liver. Expression of the beta-Klotho is necessary for the signal.Like alpha-Klotho, beta-Klotho recognizes a monosaccharide as well. Therefore, we deduced that the monosaccharide is attached to FGF19 protein. Using an antibody for unique glycan, we have identified the specific glycan of which beta-Klotho recognizes.Our study revealed how these Klotho lectins transduces the FGF signals. Furthermore, we have shown that alpha-Klotho binds to NaK-ATPase through the same recognition system. Meanwhile, it has been understood how one protein can bind to distinct binding partners, FGF family and NaK-ATPase complex.Our understandings will lead to solve unsolved questions that how physiological proteins, such as NaK-ATPase complex, are recruited to the surface membrane. That is, it would be understood that regulation of glycosylation by several glycosyl transferases regulates transports of the physiological molecules. It should be expected that more wide study to reveal biological significance of glycan would spread.

Beta-klotho是一种I型单跨膜蛋白，具有两个串联糖苷酶样结构域，主要在肝细胞中表达。基因，beta-klotho和alpha-klotho属于Klotho家族。FGF19被确定为脂质介质。控制胆汁酸合成以调节脂质摄入。 FGF19蛋白在回肠中表达，以输入信号在肝脏中。 beta-klotho的表达对于信号是必需的。例如α-klotho，β-klotho也识别单糖。因此，我们推断单糖固定在FGF19蛋白上。我们使用抗体进行独特的聚糖，已经确定了β-Klotho识别的特定聚糖。此外，我们已经证明，α-Klotho通过相同的识别系统与NAK-ATPase结合。同时，人们已经理解了一种蛋白如何与不同的结合伴侣，FGF家族和NAK-ATPase复合物结合。我们的理解将导致解决未解决的问题，即如何将生理蛋白（例如NAK-ATPase复合物）募集到表面膜上。也就是说，可以理解，通过几种糖基转移酶调节糖基化，调节生理分子的转运。应该预期的是，更多的研究揭示了聚糖的生物学意义。