Ilgü, Hüseyin; Jeckelmann, Jean-Marc; Colas, Claire; Ucurum Fotiadis, Zöhre; Schlessinger, Avner; Fotiadis, Dimitrios José (2018). Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters. International journal of molecular sciences, 19(3) MDPI 10.3390/ijms19030918
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The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures (s) of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg), agmatine, l-arginine methyl ester, and l-arginine amide. The resulting s indicated stabilization of AdiC variants upon ligand binding, in which s and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5), an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Faculty Institutions > NCCR TransCure 04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine |
UniBE Contributor: |
Ilgü, Hüseyin, Jeckelmann, Jean-Marc, Ucurum Fotiadis, Zöhre, Fotiadis, Dimitrios José |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
1661-6596 |
Publisher: |
MDPI |
Language: |
English |
Submitter: |
Barbara Franziska Järmann-Bangerter |
Date Deposited: |
27 Feb 2019 10:37 |
Last Modified: |
07 Aug 2024 15:45 |
Publisher DOI: |
10.3390/ijms19030918 |
PubMed ID: |
29558430 |
Uncontrolled Keywords: |
">l-arginine/agmatine transporter ">l-type amino acid transporter AdiC LAT1 acid resistance cancer metabolism enterobacteria melting temperature thermostability |
BORIS DOI: |
10.7892/boris.124491 |
URI: |
https://boris.unibe.ch/id/eprint/124491 |