Jeckelmann, Jean-Marc; Fotiadis, Dimitrios (2020). Sub-Nanometer Cryo-EM Density Map of the Human Heterodimeric Amino Acid Transporter 4F2hc-LAT2. International journal of molecular sciences, 21(19) MDPI 10.3390/ijms21197094
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Heterodimeric amino acid transporters (HATs) are protein complexes mediating the transport of amino acids and derivatives thereof across biological membranes. HATs are composed of two subunits, a heavy and a light chain subunit belonging to the solute carrier (SLC) families SLC3 and SLC7. The human HAT 4F2hc-LAT2 is composed of the type-II membrane N-glycoprotein 4F2hc (SCL3A2) and the L-type amino acid transporter LAT2 (SLC7A8), which are covalently linked to each other by a conserved disulfide bridge. Whereas LAT2 catalyzes substrate transport, 4F2hc is important for the successful trafficking of the transporter to the plasma membrane. The overexpression, malfunction, or absence of 4F2hc-LAT2 is associated with human diseases, and therefore, this heterodimeric complex represents a potential drug target. The recombinant human 4F2hc-LAT2 can be functionally overexpressed in the methylotrophic yeast Pichia pastoris, and the protein can be purified. Here, we present the cryo-EM density map of the human 4F2hc-LAT2 amino acid transporter at sub-nanometer resolution. A homology model of 4F2hc-LAT2 in the inward-open conformation was generated and fitted into the cryo-EM density and analyzed. In addition, disease-causing point mutations in human LAT2 were mapped on the homology model of 4F2hc-LAT2, and the possible functional implications on the molecular level are discussed.
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 09 Interdisciplinary Units > Microscopy Imaging Center (MIC) |
UniBE Contributor: |
Jeckelmann, Jean-Marc, Fotiadis, Dimitrios José |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
1422-0067 |
Publisher: |
MDPI |
Language: |
English |
Submitter: |
Barbara Franziska Järmann-Bangerter |
Date Deposited: |
20 Jan 2021 16:56 |
Last Modified: |
05 Dec 2022 15:44 |
Publisher DOI: |
10.3390/ijms21197094 |
PubMed ID: |
32993041 |
Uncontrolled Keywords: |
4F2hc L-type amino acid transporter LAT2 SLC3 SLC7 cryo-EM heteromeric amino acid transporter |
BORIS DOI: |
10.48350/150880 |
URI: |
https://boris.unibe.ch/id/eprint/150880 |
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