2 天之前 · 2019年3月14日，西湖大学生物学研究所周强研究员团队在Nature发表了题为Structure of the human LAT1–4F2hc heteromeric amino acid transporter complex的论文（第一单位为清华大学），该研究利用冷冻电镜技术，研究者首次解析了人源LAT1–4F2hc复合体整体分辨率3.3Å的 …

4F2 cell-surface antigen heavy chain is a protein that in humans is encoded by the SLC3A2 (solute carrier family 3 member 2) gene. [5][6] SLC3A2 comprises the heavy subunit of the large neutral amino acid transporter (LAT1) that is also known …

2024年5月2日 · We find that interfacial PE binding is regulated by 4F2hc-R183 and is critical for regulation of palmitoylation on neighbouring LAT1-C187. Combining native MS with mass photometry (MP), we reveal...

4F2hc是其中的重链蛋白，具有介导转运复合物细胞膜定位和维持轻链蛋白稳定性的作用。 LAT1-4F2hc在多种肿瘤细胞中过量表达，可为肿瘤细胞提供生长所需的营养物质，当抑制LAT1-4F2hc的底物运输功能时，能够明显降低肿瘤的生长速率，因此被认为是重要的抗癌靶点。

2019年3月13日 · The cryo-EM structure of the LAT1–4F2hc complex, a heteromeric amino acid transporter, is characterized, providing insights into its function and the mechanisms through which mutations of this ...

2020年11月10日 · The 4F2 cell-surface antigen heavy chain (4F2hc) is the heavy chain for LAT1 and LAT2, playing roles in plasma membrane localization of LATs 4 and required for...

LAT1 forms a heteromeric amino acid transporter complex with 4F2 cell-surface antigen heavy chain (4F2hc; also known as SLC3A2)-a type II membrane glycoprotein that is essential for the stability of LAT1 and for its localization to the plasma membrane 8,9.

Gain or loss of LAT1–4F2hc function is associated with cancer, diabetes, and immunological and neurological diseases. Hence, LAT1–4F2hc represents an attractive drug target for disease treatment.

在本项研究中，作者利用冷冻电镜技术首次解析了人源氨基酸转运蛋白LAT1-4F2hc复合物的高分辨率三维结构（图1），并且通过体外重组蛋白脂质体转运实验，首次确认4F2hc是LAT1行使底物转运功能所必需的，从而澄清了此前的争议。 此外，作者鉴定出了LAT1转运通道上的多个关键位点，在此基础上提出了4F2hc协助LAT1进行底物转运的模型，为下一步抗癌抑制剂的开发提供了重要的结构基础。...

Here, we summarize (i) structural insights that help to explain how LAT1 and 4F2hc assemble to transport amino acids across membranes, (ii) the role of LAT1-4F2hc in key metabolic signalling pathways, and (iii) how derailing these processes could contribute to diseases.