# Structure and Function of SWEET Sugar Transporters

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $323,285

## Abstract

PROJECT SUMMARY
Research over the past decade has uncovered the physiological importance and disease relevance of a large
membrane transporter/receptor superfamily, called the MtN3 clan. For example, SWEET transporters are critical
for sugar efflux and utilization; PQ-loop transporters have been linked to cystinosis and Batten disease; the
mitochondrial pyruvate carrier controls a critical branch point of the central metabolic pathway and is implicated
in cancer; and KDEL receptors are crucial for endoplasmic reticulum quality control and have been associated
with dilated cardiomyopathy. Despite these diverse and important functions, we still know little about the
molecular mechanisms of MtN3 transporters. Our overall objective is to provide structural and mechanistic
insights that elucidate the physical basis of cross-membrane transport and shed light on the physiological
functions and disease-causing malfunctions of MtN3 transporters. We will focus on SWEET sugar transporters,
the founding members of the MtN3 family, and then expand our work to include related transporter families. In
our prior research, we solved the first eukaryotic SWEET structure in an inward-open state and high-resolution
structures of bacterial SemiSWEETS in multiple conformation states, shedding light on sugar transport by
SWEETs and the alternating access mechanism more broadly. These results provide a solid foundation to further
probe the mechanisms of MtN3 transporters. In this renewal application, we propose to extend this work to: (1)
elucidate the structural basis of crosstalk and alternating access of eukaryotic SWEET; (2) dissect the substrate
selectivity of SWEET transporters; and (3) determine the structural basis of the PQ-loop transporter.
Understanding how MtN3 transporters work at the molecular level will provide rich insights into their transport
mechanisms and crosstalk. Moreover, this work will provide a blueprint to understand the function of PQ-loop
transporters and unravel the mechanisms underlying devasting lysosomal storage diseases. Ultimately, our work
will produce essential knowledge that will facilitate targeting MtN3s for therapeutics.
!

## Key facts

- **NIH application ID:** 10052029
- **Project number:** 2R01GM117108-05A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Liang Feng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $323,285
- **Award type:** 2
- **Project period:** 2016-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10052029

## Citation

> US National Institutes of Health, RePORTER application 10052029, Structure and Function of SWEET Sugar Transporters (2R01GM117108-05A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10052029. Licensed CC0.

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