Bile Acid Recognition by Mouse Ileal Bile Acid Binding Protein,ACS Chemical Biology

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Bile Acid Recognition by Mouse Ileal Bile Acid Binding Protein
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2017-11-21 00:00:00 , DOI: 10.1021/acschembio.7b00865
Mohsen Badiee ₁ , Gregory P. Tochtrop ₁

Affiliation

Ileal bile acid binding protein (I-BABP, gene name FABP6) is a component of the bile acid recycling system, expressed in the ileal enterocyte. The physiological role of I-BABP has been hypothesized to be either an intracellular buffering agent to protect against excess intracellular bile acids or separately as a modulator of bile acid controlled transcription. We investigated mouse I-BABP (mI-BABP) to understand the function of this protein family. Here, we studied energetics and site selectivity of binding with physiological bile acids using a combination of isothermal calorimetric analysis and NMR spectroscopy. We found that the most abundant bile acid in the mouse (β-muricholic acid) binds with weak affinity individually and in combination with other bile acids. Further analysis showed that mI-BABP like human I-BABP (hI-BABP) specifically recognizes the conjugated form of cholic acid:chenodeoxycholic acid (CA:CDCA) in a site-selective manner, displaying the highest affinity of any bile acid combination tested. These results indicate that I-BABP specifically recognizes the ligand combination of CDCA and CA, even in a species such as the mouse where CDCA only represents a trace component of the physiological pool. Specific and conserved recognition of the CDCA and CA ligand combination suggests that I-BABP may play a critical role in the regulation of bile acid signaling in addition to its proposed role as a buffering agent.

中文翻译：

小鼠回肠胆汁酸结合蛋白对胆汁酸的识别

回肠胆汁酸结合蛋白（I-BABP，基因名称FABP6）是胆汁酸循环系统的一个组成部分，在回肠肠上皮细胞中表达。据推测，I-BABP的生理作用是一种细胞内缓冲剂，以防止过量的细胞内胆汁酸，或分别作为胆汁酸控制的转录的调节剂。我们研究了小鼠I-BABP（mI-BABP），以了解该蛋白家族的功能。在这里，我们结合等温量热分析和NMR光谱研究了与生理胆汁酸结合的能量学和位点选择性。我们发现，小鼠中最丰富的胆汁酸（β-鼠尾草酸）会以弱亲和力单独结合并与其他胆汁酸结合。进一步的分析表明，像人I-BABP（hI-BABP）一样，mI-BABP以位点选择性方式特异性识别胆酸：鹅去氧胆酸（CA：CDCA）的共轭形式，显示了所测试的任何胆汁酸组合中的最高亲和力。这些结果表明，I-BABP即使在诸如CDCA只代表生理池痕量成分的小鼠等物种中，也能特异性识别CDCA和CA的配体组合。CDCA和CA配体组合的特异性和保守识别表明，I-BABP除了建议作为缓冲剂之外，还可能在胆汁酸信号的调节中起关键作用。这些结果表明，I-BABP即使在诸如CDCA只代表生理池痕量成分的小鼠等物种中，也能特异性识别CDCA和CA的配体组合。对CDCA和CA配体组合的特异性和保守识别表明，I-BABP除了建议作为缓冲剂之外，还可能在胆汁酸信号的调节中起关键作用。这些结果表明，I-BABP即使在诸如CDCA只代表生理池痕量成分的小鼠等物种中，也能特异性识别CDCA和CA的配体组合。CDCA和CA配体组合的特异性和保守识别表明，I-BABP除了建议作为缓冲剂之外，还可能在胆汁酸信号的调节中起关键作用。

更新日期：2017-11-21

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