Sub-Nanometer Cryo-EM Density Map of the Human Heterodimeric Amino Acid Transporter 4F2hc-LAT2.

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

[img]
Preview
Text
ijms-21-07094.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (4MB) | Preview

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)

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:

Jeckelmann, Jean-Marc and Fotiadis, Dimitrios José

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1422-0067

Publisher:

MDPI

Language:

English

Submitter:

Barbara Järmann-Bangerter

Date Deposited:

20 Jan 2021 16:56

Last Modified:

20 Jan 2021 16:56

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

Actions (login required)

Edit item Edit item
Provide Feedback