The substrate binding in the bile acid transporter ASBTYf of Yersinia frederiksenii
Xiaodong Wang, Ying Lyu, Yujia Ji, Ziyi Sun and Xiaoming Zhou [1]
Molecular Tour
Apical sodium-dependent bile acid transporter (ASBT) recycles bile acids from small intestine into enterocytes, and is a potential drug target for treating several metabolic diseases including type 2 diabetes. However, where and how bile acids bind in ASBT is unknown, which hampers our understanding toward its working mechanism.
In this study, four structures of an ASBT protein, called ASBTYf, are determined. In these structures, several ligand-like acid molecules, including a citrate, a glycine and a sulfate, bind in a putative substrate-binding pocket of the protein. The structural data are consistent with a computational model the defines the substrate-binding site, and support the binding pattern of bile acids. Functional analysis further validates the computational bile acid binding model, which provides structural insights toward its transport mechanism.
in the PDB entry 4n7x. TCA molecule (cyan stick) docked into the outward-facing central cavity viewed from the extracellular side. .
Comparison of the outward-facing ASBTYf-Pair1Linked and the inward-facing ASBTYf-Pair3Cit.
The outward-facing ASBTYf-Pair1Linked (6lh1; teal):
The inward-facing ASBTYf-Pair3Cit (6lgv; orange):
These scenes show the example of a ligand-like citrate bound in the substrate-binding site defined by the docking model. More importantly, the citrate binds to similar locations in both outward-facing and inward-facing states, mimicking the binding of bile acids.
References
- ↑ Wang X, Lyu Y, Ji Y, Sun Z, Zhou X. Substrate binding in the bile acid transporter ASBTYf from Yersinia frederiksenii. Acta Crystallogr D Struct Biol. 2021 Jan 1;77(Pt 1):117-125. doi:, 10.1107/S2059798320015004. Epub 2021 Jan 1. PMID:33404531 doi:http://dx.doi.org/10.1107/S2059798320015004
