8IDA

Overall structure of the LAT1-4F2hc bound with tyrosine

Summary for 8IDA

• Entry DOI: 10.2210/pdb8ida/pdb
• EMDB information: 35361
• Descriptor: 4F2 cell-surface antigen heavy chain, Large neutral amino acids transporter small subunit 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: complex, membrane protein, amino acid
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 129226.52

Authors

Yan, R.H.,Li, Y.N.,Shi, T.H. (deposition date: 2023-02-12, release date: 2024-07-10, Last modification date: 2025-11-26)

Primary citation

Yang, H.,Shi, T.,Dong, J.,Zhang, T.,Li, Y.,Guo, Y.,Yuan, Y.,Yang, L.,Dong, J.T.,Yan, R.
Structural insights into the substrate transport mechanism of the amino acid transporter complex.
J.Biol.Chem., 301:110569-110569, 2025

PubMed Abstract: The -type amino acid transporter 1 (LAT1), in complex with its ancillary protein 4F2hc, mediates the sodium-independent antiport of large neutral amino acids across the plasma membrane. LAT1 preferentially transports substrates, such as -leucine, -tyrosine, and -tryptophan, thyroid hormones, and drugs like 3,4-dihydroxyphenylalanine. Its pivotal role in cancer development and progression has established LAT1 as a promising therapeutic target. While prior studies have resolved the LAT1-4F2hc architecture and inhibitor interactions, the molecular basis of LAT1 substrate selectivity remains elusive. Here, we present the cryo-EM structures of LAT1-4F2hc bound to -tyrosine, -tryptophan, -leucine, and 3,4-dihydroxyphenylalanine, revealing distinct substrate binding modes. Comparative structural analysis highlights differences between LAT1 and LAT2 in substrate coordination, driven by key residues near the binding pocket that influence transport efficiency. These findings advance our mechanistic understanding of the LAT1-4F2hc complex and provide valuable insights for structure-based drug design targeting LAT1.

PubMed: 40780412
DOI: 10.1016/j.jbc.2025.110569

Experimental method

ELECTRON MICROSCOPY (3.2 Å)