8U3H

Structure of Fmoc-Leu-OH bound Sialin

8U3H の概要

• エントリーDOI: 10.2210/pdb8u3h/pdb
• EMDBエントリー: 41862
• 分子名称: Sialin, Fluorenylmethyloxycarbonyl chloride, LEUCINE (3 entities in total)
• 機能のキーワード: transporter, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 56071.01

構造登録者

Schmiege, P.,Li, X. (登録日: 2023-09-07, 公開日: 2024-05-29, 最終更新日: 2024-12-11)

主引用文献

Schmiege, P.,Donnelly, L.,Elghobashi-Meinhardt, N.,Lee, C.H.,Li, X.
Structure and inhibition of the human lysosomal transporter Sialin.
Nat Commun, 15:4386-4386, 2024

PubMed Abstract: Sialin, a member of the solute carrier 17 (SLC17) transporter family, is unique in its ability to transport not only sialic acid using a pH-driven mechanism, but also transport mono and diacidic neurotransmitters, such as glutamate and N-acetylaspartylglutamate (NAAG), into synaptic vesicles via a membrane potential-driven mechanism. While most transporters utilize one of these mechanisms, the structural basis of how Sialin transports substrates using both remains unclear. Here, we present the cryogenic electron-microscopy structures of human Sialin: apo cytosol-open, apo lumen-open, NAAG-bound, and inhibitor-bound. Our structures show that a positively charged cytosol-open vestibule accommodates either NAAG or the Sialin inhibitor Fmoc-Leu-OH, while its luminal cavity potentially binds sialic acid. Moreover, functional analyses along with molecular dynamics simulations identify key residues in binding sialic acid and NAAG. Thus, our findings uncover the essential conformational states in NAAG and sialic acid transport, demonstrating a working model of SLC17 transporters.

PubMed: 38782953
DOI: 10.1038/s41467-024-48535-3

実験手法

ELECTRON MICROSCOPY (3.67 Å)