瑞典斯德哥尔摩大学David Drew研究团队报道了SLC35B1对内质网ATP转运的影响。这一研究成果发表在2025年5月21日出版的国际学术期刊《自然》上。

在这里，该课题组研究人员报道了人类SLC35B1不结合核苷酸糖，但确实执行严格的ATP/ADP交换，其摄取动力学与ATP进入粗内质网微粒体的进口一致。CRISPR-Cas9细胞系敲除表明，SLC35B1具有细胞生长最基本的SLC转运体，与其提出的生理功能一致。研究组进一步确定了人类SLC35B1与Fv片段复合物的7个低温电镜结构，这些复合物在转运循环的所有主要构象中要么与ATP类似物结合，要么与ADP结合。该课题组观察到核苷酸垂直重新定位到大约6.5在易位过程中，同时保持与柔性底物结合位点的关键相互作用。课题组研究人员得出结论，SLC35B1通过逐步ATP转运机制起作用，这是先前描述的SLC转运体底物转运模型。

研究人员表示，线粒体中产生的ATP由SLC25家族的ADP/ATP载体输出。内质网（ER）不能合成ATP，但会输入胞质ATP，为蛋白质折叠、质量控制和运输提供能量。最近有人提出，核苷酸糖转运蛋白家族的成员，称为SLC35B1（也称为AXER），不是核苷酸糖转运蛋白，而是长期追求的ATP4 ER进口商。

附：英文原文

Title: Stepwise ATP translocation into the endoplasmic reticulum by human SLC35B1

Author: Gulati, Ashutosh, Ahn, Do-Hwan, Suades, Albert, Hult, Yurie, Wolf, Gernot, Iwata, So, Superti-Furga, Giulio, Nomura, Norimichi, Drew, David

Issue&Volume: 2025-05-21

Abstract: ATP generated in the mitochondria is exported by an ADP/ATP carrier of the SLC25 family1. The endoplasmic reticulum (ER) cannot synthesize ATP but must import cytoplasmic ATP to energize protein folding, quality control and trafficking2,3. 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 ATP4. 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 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.

DOI: 10.1038/s41586-025-09069-w

Source: https://www.nature.com/articles/s41586-025-09069-w