9GS3

Cryo-EM structure of human SLC35B1-E33A variant with ADP in inward facing conformation

9GS3 の概要

• エントリーDOI: 10.2210/pdb9gs3/pdb
• EMDBエントリー: 51538
• 分子名称: SLC35B1-E33A inward facing conformation, Maltodextrin-binding protein, ADENOSINE-5'-DIPHOSPHATE (3 entities in total)
• 機能のキーワード: atp:adp exchanger, axer, er membrane protein, transport protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 104689.20

構造登録者

Gulati, A.,Ahn, D.,Suades, A.,Drew, D. (登録日: 2024-09-13, 公開日: 2025-05-21, 最終更新日: 2025-08-20)

主引用文献

Gulati, A.,Ahn, D.H.,Suades, A.,Hult, Y.,Wolf, G.,Iwata, S.,Superti-Furga, G.,Nomura, N.,Drew, D.
Stepwise ATP translocation into the endoplasmic reticulum by human SLC35B1.
Nature, 643:855-864, 2025

PubMed Abstract: ATP generated in the mitochondria is exported by an ADP/ATP carrier of the SLC25 family. The endoplasmic reticulum (ER) cannot synthesize ATP but must import cytoplasmic ATP to energize protein folding, quality control and trafficking. It was recently proposed that a member of the nucleotide sugar transporter family, termed SLC35B1 (also known as AXER), is not a nucleotide sugar transporter but a long-sought-after ER importer of ATP. Here we report that human SLC35B1 does not bind nucleotide sugars but indeed executes strict ATP/ADP exchange with uptake kinetics consistent with the import of ATP into crude ER microsomes. A CRISPR-Cas9 cell-line knockout demonstrated that SLC35B1 clusters with the most essential SLC transporters for cell growth, consistent with its proposed physiological function. We have further determined seven cryogenic electron microscopy structures of human SLC35B1 in complex with an Fv fragment and either bound to an ATP analogue or ADP in all major conformations of the transport cycle. We observed that nucleotides were vertically repositioned up to approximately 6.5 Å during translocation while retaining key interactions with a flexible substrate-binding site. We conclude that SLC35B1 operates by a stepwise ATP translocation mechanism, which is a previously undescribed model for substrate translocation by an SLC transporter.

PubMed: 40399679
DOI: 10.1038/s41586-025-09069-w

実験手法

ELECTRON MICROSCOPY (3.15 Å)