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-Structure paper
タイトル | Cryo-EM structure of the human L-type amino acid transporter 1 in complex with glycoprotein CD98hc. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 26, Issue 6, Page 510-517, Year 2019 |
掲載日 | 2019年6月3日 |
著者 | Yongchan Lee / Pattama Wiriyasermkul / Chunhuan Jin / Lili Quan / Ryuichi Ohgaki / Suguru Okuda / Tsukasa Kusakizako / Tomohiro Nishizawa / Kazumasa Oda / Ryuichiro Ishitani / Takeshi Yokoyama / Takanori Nakane / Mikako Shirouzu / Hitoshi Endou / Shushi Nagamori / Yoshikatsu Kanai / Osamu Nureki / |
PubMed 要旨 | The L-type amino acid transporter 1 (LAT1 or SLC7A5) transports large neutral amino acids across the membrane and is crucial for brain drug delivery and tumor growth. LAT1 forms a disulfide-linked ...The L-type amino acid transporter 1 (LAT1 or SLC7A5) transports large neutral amino acids across the membrane and is crucial for brain drug delivery and tumor growth. LAT1 forms a disulfide-linked heterodimer with CD98 heavy chain (CD98hc, 4F2hc or SLC3A2), but the mechanism of assembly and amino acid transport are poorly understood. Here we report the cryo-EM structure of the human LAT1-CD98hc heterodimer at 3.3-Å resolution. LAT1 features a canonical Leu T-fold and exhibits an unusual loop structure on transmembrane helix 6, creating an extended cavity that might accommodate bulky amino acids and drugs. CD98hc engages with LAT1 through the extracellular, transmembrane and putative cholesterol-mediated interactions. We also show that two anti-CD98 antibodies recognize distinct, multiple epitopes on CD98hc but not its glycans, explaining their robust reactivities. These results reveal the principles of glycoprotein-solute carrier assembly and provide templates for improving preclinical drugs and antibodies targeting LAT1 or CD98hc. |
リンク | Nat Struct Mol Biol / PubMed:31160781 |
手法 | EM (単粒子) |
解像度 | 3.31 - 4.1 Å |
構造データ | |
化合物 | ChemComp-CLR: ChemComp-NAG: |
由来 |
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キーワード | MEMBRANE PROTEIN/IMMUNE SYSTEM / Transporter / Glycoprotein / Complex / MEMBRANE PROTEIN / MEMBRANE PROTEIN-IMMUNE SYSTEM complex |