Unveiling the Ro60-Ro52 complex.

IF 3.8 3区 生物学 Q1 BIOLOGY
EXCLI Journal Pub Date : 2024-06-10 eCollection Date: 2024-01-01 DOI:10.17179/excli2024-7141
Laura R Rodríguez, Jesus Vicente de Julián-Ortiz, Fernando Rubio de la Rúa, Augusto Juste-Dolz, Ángel Maquieira, Haydar A Mohammad-Salim, Sofiane Benmetir, Federico V Pallardó, Pilar González-Cabo, David Gimenez-Romero
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Abstract

The coexistence within a subcellular complex of inter-cellular proteins Ro60, responsible for preserving ncRNA quality, and Ro52, involved in intracellular proteolysis, has been a subject of ongoing debate. Employing molecular docking in tandem with experimental methods like Quartz Crystal Microbalance with Dissipation (QCM-D), Proximity Ligation Assay (PLA), and Indirect Immunofluorescence (IIF), we reveal the presence of Ro60 associating with Ro52 within the cytoplasm. This result unveils the formation of a weak transient complex with a Ka ≈ (3.7 ± 0.3) x 106 M-1, where the toroid-shaped Ro60 structure interacts with the Ro52's Fc receptor, aligning horizontally within the PRY-SPRY domains of the Ro52's homodimer. The stability of this complex relies on the interaction between Ro52 chain A and specific Ro60 residues, such as K133, W177, or L185, vital in the Ro60-YRNA bond. These findings bridge the role of Ro60 in YRNA management with Ro52's function in intracellular proteolysis, emphasizing the potential impact of transient complexes on cellular pathways. See also the graphical abstract(Fig. 1).

揭开 Ro60-Ro52 建筑群的神秘面纱。
细胞间蛋白 Ro60 负责保持 ncRNA 的质量,而 Ro52 则参与细胞内蛋白水解,两者在亚细胞复合物中的共存一直是争论不休的话题。通过分子对接以及石英晶体微天平消散法(QCM-D)、邻接法(PLA)和间接免疫荧光法(IIF)等实验方法,我们揭示了 Ro60 与 Ro52 在细胞质中的联系。这一结果揭示了一种弱瞬时复合物的形成,其 Ka ≈ (3.7 ± 0.3) x 106 M-1,其中环状的 Ro60 结构与 Ro52 的 Fc 受体相互作用,在 Ro52 同源二聚体的 PRY-SPRY 结构域内水平排列。该复合物的稳定性依赖于 Ro52 链 A 与特定 Ro60 残基(如 K133、W177 或 L185)之间的相互作用,这些残基在 Ro60-YRNA 键中至关重要。这些发现将 Ro60 在 YRNA 管理中的作用与 Ro52 在细胞内蛋白水解中的功能联系起来,强调了瞬时复合物对细胞通路的潜在影响。另见图表摘要(图 1)。
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来源期刊
EXCLI Journal
EXCLI Journal BIOLOGY-
CiteScore
8.00
自引率
2.20%
发文量
65
审稿时长
6-12 weeks
期刊介绍: EXCLI Journal publishes original research reports, authoritative reviews and case reports of experimental and clinical sciences. The journal is particularly keen to keep a broad view of science and technology, and therefore welcomes papers which bridge disciplines and may not suit the narrow specialism of other journals. Although the general emphasis is on biological sciences, studies from the following fields are explicitly encouraged (alphabetical order): aging research, behavioral sciences, biochemistry, cell biology, chemistry including analytical chemistry, clinical and preclinical studies, drug development, environmental health, ergonomics, forensic medicine, genetics, hepatology and gastroenterology, immunology, neurosciences, occupational medicine, oncology and cancer research, pharmacology, proteomics, psychiatric research, psychology, systems biology, toxicology
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