# Structural and Functional Underpinnings of Proton Coupling in Glutamate Transporters

> **NIH NIH F31** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $46,752

## Abstract

PROJECT ABSTRACT
 Glutamate is the primary excitatory neurotransmitter in the brain and is necessary for several crucial
brain functions. Mammalian glutamate transporters, or excitatory amino acid transporters (EAATs), are
responsible for rapidly clearing excessive glutamate to prevent excitotoxicity and in shaping synaptic
transmission. Therefore, EAATs dysfunction is often linked to neurological pathologies. Most of our
understanding resulted from studying archaeal homologue, GltPh from Pyrococcus horikoshii. In EAATs,
substrate transport is coupled to three sodiums, one proton, and the countertransport of a potassium ion, while
GltPh is exclusively sodium-coupled, so there is limited insight as to how protons bind, and the mechanism by
which they drive transport.
 Bacterial homologue, GltTBc from Bacillus caldotenax, is driven by symport of protons rather than
sodium ions. These homologues share a similar trimeric structure but have different ion-coupling specificity.
There is no high-resolution structure for GltTBc or any other proton-coupled transporter of this family. The goal
of my first Aim is to obtain a high-resolution structure of GltTBc to both identify potential protonation sites and
understand the structural basis of specificity during ion coupling. To determine the role of protons during
substrate transport in GltTBc, Aim 2 will elucidate whether protons drive glutamate binding or translocation and
understand the molecular basis of proton coupling.
 Under this fellowship, I will have access to consult with leading researchers from Weill Cornell and
associated core research facilities. Being in the middle of the “corridor of science”, which is composed of Weill
Cornell, The Rockefeller Institution, and Memorial Sloan Kettering Cancer Center, will provide me with ample
opportunities and resources to not only enhance my technical skills, but allow me to present and communicate
my work to the scientific community. This will be aided by my PI’s recent advancements in establishing the
Molecular Biophysics Training Program, which provides another source of support, community, and expertise
within the Tri-Institiutional campus.

## Key facts

- **NIH application ID:** 10497900
- **Project number:** 5F31GM143878-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Yessenia Lopez
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 5
- **Project period:** 2021-09-20 → 2023-09-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10497900

## Citation

> US National Institutes of Health, RePORTER application 10497900, Structural and Functional Underpinnings of Proton Coupling in Glutamate Transporters (5F31GM143878-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10497900. Licensed CC0.

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