Molecular basis of SLC19A1-mediated folate and cyclic dinucleotide transport

Related Experiment Video

Updated: May 17, 2025

Author Spotlight: Expression and Purification of Human Solute Carrier Transporters Using Codon-Optimized Genes
07:10

Author Spotlight: Expression and Purification of Human Solute Carrier Transporters Using Codon-Optimized Genes

Published on: September 29, 2023

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Qixiang Zhang1, Xuyuan Zhang2, Kexin Liu2,3

  • 1Key Laboratory of Molecular Medicine and Biotherapy, Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing, China.

Nature Communications
|April 2, 2025
PubMed

Insights

The solute carrier protein SLC19A1

Area of Science:

  • Structural Biology
  • Molecular Transport
  • Drug Discovery

Background:

  • Solute carrier protein SLC19A1 transports vital nutrients and drugs.
  • Understanding SLC19A1's conformational dynamics and substrate transport is crucial.
  • Previous studies focused on the inward-open state, leaving outward-open mechanisms unclear.

Purpose of the Study:

  • To elucidate the outward-open state structures of human SLC19A1 (hSLC19A1).
  • To reveal mechanisms of substrate recognition and conformational changes during transport.
  • To understand the binding of cyclic dinucleotides (CDNs) and antifolates.

Main Methods:

  • Antibody-facilitated conformation screening.
  • Cryo-electron microscopy (cryo-EM) of hSLC19A1.
  • Functional assays to validate structural findings.

Main Results:

  • Determined cryo-EM structures of hSLC19A1 in the outward-open state.
  • Identified specific binding pockets for folates, antifolates, and CDNs.
  • Observed monomeric binding of CDNs in the outward-open state, differing from inward-open states.

Conclusions:

  • Provided detailed insights into hSLC19A1 substrate recognition and transport mechanisms.
  • Revealed distinct binding modes for CDNs in different conformational states.
  • Established a framework for developing novel antifolate drugs and CDN-based therapies.

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