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MEMBRANE TRANSPORT

Insights into L-type heteromeric amino acid transporters

Nature Structural & Molecular Biology volume 26, pages 395–396 (2019)Cite this article

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Two recent cryo-EM structures of the human L-type heteromeric amino acid transporter LAT1–CD98hc reveal surprising new insights into both amino acid transport in the human body and the roles of CD98hc as a cell-surface antigen and trafficking chaperone.

Mammalian amino acid transporters are categorized into several transport systems on the basis of their substrate selectivity and mechanism. The uptake and distribution of dietary amino acids is carried out predominantly by so-called ‘system-L transporters’, which mediate Na+-independent transport of large amino acids across the plasma membrane3. Among these, LAT1 (L-type amino acid transporter 1; also known as SLC7A5) has attracted the most interest due to its prominent role in stimulating cancer-cell growth through the uptake of l-leucine4, supplying thyroid hormones to developing fetuses and transporting L-DOPA (L-3,4-dihydroxyphenylalanine) and other neurological drugs across the blood–brain barrier5. As a subunit of a heteromeric amino acid transporter, LAT1, referred to as the ‘light’ subunit, associates with a second protein, CD98hc (also known as 4F2hc or SLC3A2), referred to as the ‘heavy’ subunit. CD98hc, with molecular weight of 85 kDa in its mature form, comprises a single transmembrane domain and a large extracellular domain that is heavily glycosylated6.

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Fig. 1: Physiological role of the LAT1–CD98hc heteromeric amino acid transporter.
Fig. 2: Structure of the LAT1–CD98hc complex.

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  1. Department of Biochemistry, University of Oxford, Oxford, UK

    Simon Newstead

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  1. Simon Newstead
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Correspondence to Simon Newstead.

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Newstead, S. Insights into L-type heteromeric amino acid transporters. Nat Struct Mol Biol 26, 395–396 (2019). https://doi.org/10.1038/s41594-019-0240-z

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