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Volta Phase Plate Cryo-EM Structure of the Human Heterodimeric Amino Acid Transporter 4F2hc-LAT2

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Jeckelmann Jean-Marc, Fotiadis Dimitrios,
Project Direct electron detector and phase plate for cryo-transmission electron microscopy of biological samples
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Original article (peer-reviewed)

Journal International Journal of Molecular Sciences
Volume (Issue) 20(4)
Page(s) 931 - 931
Title of proceedings International Journal of Molecular Sciences
DOI 10.3390/ijms20040931

Open Access

URL http://doi.org/10.3390/ijms20040931
Type of Open Access Publisher (Gold Open Access)

Abstract

Heteromeric amino acid transporters (HATs) are protein complexes that catalyze the transport of amino acids across plasma membranes. HATs are composed of two subunits, a heavy and a light subunit, which belong to the solute carrier (SLC) families SLC3 and SLC7. The two subunits are linked by a conserved disulfide bridge. Several human diseases are associated with loss of function or overexpression of specific HATs making them drug targets. The human HAT 4F2hc-LAT2 (SLC3A2-SLC7A8) is specific for the transport of large neutral L-amino acids and specific amino acid-related compounds. Human 4F2hc-LAT2 can be functionally overexpressed in the methylotrophic yeast Pichia pastoris and pure recombinant protein purified. Here we present the first cryo-electron microscopy (cryo-EM) 3D-map of a HAT, i.e., of the human 4F2hc-LAT2 complex. The structure could be determined at ~13 Å resolution using direct electron detector and Volta phase plate technologies. The 3D-map displays two prominent densities of different sizes. The available X-ray structure of the 4F2hc ectodomain fitted nicely into the smaller density revealing the relative position of 4F2hc with respect to LAT2 and the membrane plane.
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