# Principles of selectivity and translocation in transition metal transporter

> **NIH NIH R35** · UNIVERSITY OF TEXAS DALLAS · 2021 · $246,400

## Abstract

Abstract
Transition metals, such as iron, copper, and zinc, are essential trace elements for life, playing fundamental
catalytic, structural and signaling functions. Transmembrane transporters that regulate the vectorial metal uptake
and extrusion across cellular membranes play a gatekeeper role in controlling metal homeostasis. Their activity
guarantees that metal levels are tightly regulated to meet indispensable cellular requirements without reaching
toxic levels.
The parent MIRA project targets primary active transition metal pumps and solute carriers (SLC) towards: (i)
investigating the principles of metal selectivity for first, second- and third- row transition metals and (ii) their metal
coordination chemistry; (iii) determining the metal translocation pathway; (iv) addressing the mechanisms of
energy transduction processes at a molecular level. We investigate known and novel transporter families
involved in metal homeostasis and disease progression including: 1) P1B-type ATPases, primary active
transporters controlling intracellular copper levels in humans, and modulating the concentrations of copper and
other transition metals in pathogenic bacteria; 2) TMEM205, a novel human transporter involved in copper
extrusion and anti-cancer Pt-complexes transport and resistance; 3) IroT transporters, putative iron-regulated
solute carriers responsible for iron(II) acquisition and virulence in pathogenic prokaryotes.
In this proposal we propose the acquisition of a Biacore T200 Surface Plasmon Resonance instrument to identify
and characterize the interactions between transporters and molecular partners responsible for metal delivery
and uptake to/from the investigated transporters. This instrumentation will be utilized to quantitatively determine
kinetic, affinity, specificity, selectivity, and thermodynamic parameters of biomolecular interactions with metal-
chaperone donors/acceptors, and screen small molecule libraries to identify novel transporter modulators. The
unit features a sample recovery modality in the analyte dissociation phase and will be integrated in a proteomic
and metallomic workflow to allow identification, characterization and metal speciation of novel binders from cell
extracts and fractionated lysates. The implementation of this instrument in our experimental workflow is expected
to provide unprecedented molecular insights in key pathways responsible for metal delivery and activation of
transmembrane metal transporters in prokaryotes and eukaryotes.

## Key facts

- **NIH application ID:** 10389352
- **Project number:** 3R35GM128704-04S1
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Gabriele Meloni
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $246,400
- **Award type:** 3
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10389352

## Citation

> US National Institutes of Health, RePORTER application 10389352, Principles of selectivity and translocation in transition metal transporter (3R35GM128704-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10389352. Licensed CC0.

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