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Volume 8 Supplement 1

Annual Meeting of the Study Group Neurochemistry. International Conference of the Gesellschaft für Biochemie und Molekularbiologie 2006 (GBM 2006): Molecular pathways in health and disease of the nervous system

Identification of small aromatic ligands to GABA-A receptor associated protein GABARAP

BMC Neuroscience volume 8, Article number: P20 (2007) Cite this article

Type-A receptors for the neurotransmitter GABA (gamma-aminobutyric acid) are ligand-gated chloride channels that mediate inhibitory neuro-transmission. The 14 kDa GABA-A receptor associated protein GABARAP interacts with the gamma2 subunit of GABA-A receptor and modulates channel kinetics and promotes channel clustering. GABARAP is involved in receptor trafficking and targeting to GABAergic synapses.

With Phage Display methods we identified peptides with micromolar affinity for GABARAP. Although exhibiting great sequence diversity, the most prominent common feature of the selected peptides was a tryptophan residue occurring in all peptides. This lead us to further investigate the role of this tryptophan residue in GABARAP-ligand interactions.

We used saturation transfer difference NMR (STDNMR) in order to identify tryptophan-derived small aromatic molecules which interact with GABARAP. Chemical shift perturbation and J-surface analysis allowed for mapping of the indole moiety's binding site to GABARAP.

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Authors and Affiliations

  1. Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

    Thomas Stangler, Jeaninne Mohrlüder, Yvonne Hoffmann & Dieter Willbold

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  1. Thomas Stangler
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  2. Jeaninne Mohrlüder
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  3. Yvonne Hoffmann
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  4. Dieter Willbold
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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Stangler, T., Mohrlüder, J., Hoffmann, Y. et al. Identification of small aromatic ligands to GABA-A receptor associated protein GABARAP. BMC Neurosci 8 (Suppl 1), P20 (2007). https://doi.org/10.1186/1471-2202-8-S1-P20

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  • DOI: https://doi.org/10.1186/1471-2202-8-S1-P20

Keywords

  • Tryptophan Residue
  • GABAergic Synapse
  • Saturation Transfer
  • Gamma2 Subunit
  • Neurotransmitter Gaba

BMC Neuroscience

ISSN: 1471-2202

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