Disorder-mediated interactions target proteins to specific condensates

IF 14.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cell Pub Date : 2024-09-03 DOI:10.1016/j.molcel.2024.08.017

Nancy De La Cruz, Prashant Pradhan, Reshma T. Veettil, Brooke A. Conti, Mariano Oppikofer, Benjamin R. Sabari

{"title":"Disorder-mediated interactions target proteins to specific condensates","authors":"Nancy De La Cruz, Prashant Pradhan, Reshma T. Veettil, Brooke A. Conti, Mariano Oppikofer, Benjamin R. Sabari","doi":"10.1016/j.molcel.2024.08.017","DOIUrl":null,"url":null,"abstract":"<p>Selective compartmentalization of cellular contents is fundamental to the regulation of biochemistry. Although membrane-bound organelles control composition by using a semi-permeable barrier, biomolecular condensates rely on interactions among constituents to determine composition. Condensates are formed by dynamic multivalent interactions, often involving intrinsically disordered regions (IDRs) of proteins, yet whether distinct compositions can arise from these dynamic interactions is not known. Here, by comparative analysis of proteins differentially partitioned by two different condensates, we find that distinct compositions arise through specific IDR-mediated interactions. The IDRs of differentially partitioned proteins are necessary and sufficient for selective partitioning. Distinct sequence features are required for IDRs to partition, and swapping these sequence features changes the specificity of partitioning. Swapping whole IDRs retargets proteins and their biochemical activity to different condensates. Our results demonstrate that IDR-mediated interactions can target proteins to specific condensates, enabling the spatial regulation of biochemistry within the cell.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"66 1","pages":""},"PeriodicalIF":14.5000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.molcel.2024.08.017","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Selective compartmentalization of cellular contents is fundamental to the regulation of biochemistry. Although membrane-bound organelles control composition by using a semi-permeable barrier, biomolecular condensates rely on interactions among constituents to determine composition. Condensates are formed by dynamic multivalent interactions, often involving intrinsically disordered regions (IDRs) of proteins, yet whether distinct compositions can arise from these dynamic interactions is not known. Here, by comparative analysis of proteins differentially partitioned by two different condensates, we find that distinct compositions arise through specific IDR-mediated interactions. The IDRs of differentially partitioned proteins are necessary and sufficient for selective partitioning. Distinct sequence features are required for IDRs to partition, and swapping these sequence features changes the specificity of partitioning. Swapping whole IDRs retargets proteins and their biochemical activity to different condensates. Our results demonstrate that IDR-mediated interactions can target proteins to specific condensates, enabling the spatial regulation of biochemistry within the cell.

Abstract Image

查看原文本刊更多论文

无序介导的相互作用将蛋白质锁定在特定凝聚物上

细胞内容物的选择性分隔是调节生物化学的基础。虽然膜结合细胞器利用半透屏障控制成分，但生物分子凝聚体则依靠成分之间的相互作用来决定成分。凝结物是由动态多价相互作用形成的，通常涉及蛋白质的固有无序区（IDR），但这些动态相互作用是否会产生不同的成分尚不清楚。在这里，我们通过对两种不同凝聚物中不同分区的蛋白质进行比较分析，发现不同的组成是通过特定的 IDR 介导的相互作用产生的。不同分区蛋白质的 IDR 是选择性分区的必要条件和充分条件。IDR需要不同的序列特征才能分区，而交换这些序列特征会改变分区的特异性。交换整个 IDR 可将蛋白质及其生化活性重新定向到不同的凝聚物中。我们的研究结果表明，IDR 介导的相互作用可将蛋白质定向到特定的凝聚体，从而实现细胞内生化的空间调控。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Molecular Cell 生物-生化与分子生物学

CiteScore

26.00

自引率

3.80%

发文量

389

审稿时长

1 months

期刊介绍： Molecular Cell is a companion to Cell, the leading journal of biology and the highest-impact journal in the world. Launched in December 1997 and published monthly. Molecular Cell is dedicated to publishing cutting-edge research in molecular biology, focusing on fundamental cellular processes. The journal encompasses a wide range of topics, including DNA replication, recombination, and repair; Chromatin biology and genome organization; Transcription; RNA processing and decay; Non-coding RNA function; Translation; Protein folding, modification, and quality control; Signal transduction pathways; Cell cycle and checkpoints; Cell death; Autophagy; Metabolism.