# Structural Biology of the Apical Bile Acid Transporter

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $350,326

## Abstract

Bile acids have been recognized to function as second messengers and hormones, with
clinical implications in glucose, lipid and energy metabolism. The human apical sodium-
dependent bile acid transporter (hASBT) plays a key role in the enterohepatic recycling
of bile salts, cholesterol homeostasis, and serves as a molecular target for
hypercholesterolemic agents and pharmaceutical prodrug strategies. Despite its clinical
significance, ASBT is poorly characterized at the molecular level. The proposed
research will focus on the structural biology of ASBT. Two recent bacterial crystal
structures claim evolutionary relatedness to hASBT, yet their topology is in clear contrast
to biochemical data in the literature. The current proposal directly confronts this
controversy and our plan to advance understanding of bile acid transporter structure,
function and regulation is organized around the following aims: 1) Do bacterial
transporter structures provide representative structural models for eukaryotic
SLC10 orthologs? wherein we hypothesize that analysis of genetic ancestry and
substrate phenotype of orthologs can determine evolutionary and structural relatedness
of (putative) prokaryotic and eukaryotic SLC10A family members; further, we aim to
express, purify, crystallize and determine the x-ray structure of eukaryotic SLC10A
orthologs; 2) To characterize and map the functional regulation and modulation of
hASBT expression; where we will apply a proteomics approach to determining post-
translational modifications temporally. Based on our preliminary data we will further
investigate the organization of hASBT in higher-order dimers or multimers as a way of
controlling function. Information gained by these studies will significantly increase our
understanding of the structural interactions that drive bile acid transport and further our
structural knowledge of solute carrier (SLC) proteins in general. Additionally, it may aid
future development of specific therapeutic strategies against hypercholesterolemia and
related cardiovascular and metabolic diseases.

## Key facts

- **NIH application ID:** 9994279
- **Project number:** 5R01DK061425-15
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** PETER W SWAAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $350,326
- **Award type:** 5
- **Project period:** 2003-05-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994279

## Citation

> US National Institutes of Health, RePORTER application 9994279, Structural Biology of the Apical Bile Acid Transporter (5R01DK061425-15). Retrieved via AI Analytics 2026-07-20 from https://api.ai-analytics.org/grant/nih/9994279. Licensed CC0.

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