The solute carrier superfamily interactome.

IF 8.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Systems Biology Pub Date : 2025-06-01 Epub Date: 2025-05-12 DOI:10.1038/s44320-025-00109-1

Fabian Frommelt, Rene Ladurner, Ulrich Goldmann, Gernot Wolf, Alvaro Ingles-Prieto, Eva Lineiro-Retes, Zuzana Gelová, Ann-Katrin Hopp, Eirini Christodoulaki, Shao Thing Teoh, Philipp Leippe, Brianda L Santini, Manuele Rebsamen, Sabrina Lindinger, Iciar Serrano, Svenja Onstein, Christoph Klimek, Barbara Barbosa, Anastasiia Pantielieieva, Vojtech Dvorak, Thomas J Hannich, Julian Schoenbett, Gilles Sansig, Tamara A M Mocking, Jasper F Ooms, Adriaan P IJzerman, Laura H Heitman, Peter Sykacek, Juergen Reinhardt, André C Müller, Tabea Wiedmer, Giulio Superti-Furga

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引用次数: 0

Abstract

Solute carrier (SLC) transporters form a protein superfamily that enables transmembrane transport of diverse substrates including nutrients, ions and drugs. There are about 450 different SLCs, residing in a variety of subcellular membranes. Loss-of-function of an unusually high proportion of SLC transporters is genetically associated with a plethora of human diseases, making SLCs a rapidly emerging but challenging drug target class. Knowledge of their protein environment may elucidate the molecular basis for their functional integration with metabolic and cellular pathways and help conceive pharmacological interventions based on modulating proteostatic regulation. We aimed at obtaining a global survey of the SLC-protein interaction landscape and mapped the protein-protein interactions of 396 SLCs by interaction proteomics. We employed a functional assessment based on RNA interference of interactors in combination with measurement of protein stability and localization. As an example, we detail the role of a SLC16A6 phospho-degron and the contributions of PDZ-domain proteins LIN7C and MPP1 to the trafficking of SLC43A2. Overall, our work offers a resource for SLC-protein interactions for the scientific community.

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溶质载体超族相互作用。

溶质载体（SLC）转运蛋白形成一个蛋白质超家族，能够跨膜运输多种底物，包括营养物质、离子和药物。大约有450种不同的SLCs存在于不同的亚细胞膜中。异常高比例的SLC转运体功能丧失与大量人类疾病在遗传上相关，这使得SLC成为一个迅速出现但具有挑战性的药物靶点类别。了解它们的蛋白质环境可以阐明它们与代谢和细胞途径功能整合的分子基础，并有助于构思基于调节蛋白质抑制调节的药理学干预。我们旨在获得slc -蛋白相互作用格局的全球调查，并通过相互作用蛋白质组学绘制了396种slc的蛋白相互作用图谱。我们采用了基于相互作用物的RNA干扰的功能评估，结合蛋白质稳定性和定位的测量。作为一个例子，我们详细介绍了SLC16A6磷酸化降解子的作用以及pdz结构域蛋白LIN7C和MPP1在SLC43A2转运中的作用。总的来说，我们的工作为科学界提供了slc -蛋白相互作用的资源。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Systems Biology 生物-生化与分子生物学

CiteScore

18.50

自引率

1.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Systems biology is a field that aims to understand complex biological systems by studying their components and how they interact. It is an integrative discipline that seeks to explain the properties and behavior of these systems. Molecular Systems Biology is a scholarly journal that publishes top-notch research in the areas of systems biology, synthetic biology, and systems medicine. It is an open access journal, meaning that its content is freely available to readers, and it is peer-reviewed to ensure the quality of the published work.