未加工的BMP9前体是其活性生长因子的内在拮抗剂

IF 4.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Structure Pub Date : 2025-05-23 DOI:10.1016/j.str.2025.04.021

Weida Zhang, Yuanyuan Zhang, Weidong Mao, Tao Huang, Xinrong Yu, Xiaohong Qin, Li-Zhi Mi

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引用次数: 0

摘要

BMP9是TGFβ超家族的成员，在血管生成、组织发育和先天免疫中起着至关重要的作用。BMP9信号的失调与多种疾病有关。与潜在的tgf β不同，BMP9是作为前体产生的，被加工成活性的前蛋白复合物。然而，控制前体活性及其生物学功能的调节机制在很大程度上尚未被探索。在这项研究中，我们证明了未加工的BMP9前体在血管生成和成骨过程中作为其前蛋白的内在拮抗剂。这种抑制作用通过与受体ENG和ALK1的竞争性结合发生。我们还确定了这些受体识别前体的结构要求。我们的研究结果揭示了BMP9前体的功能及其在生长因子信号传导中的调节机制，对发育生物学和临床干预具有重要意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Unprocessed BMP9 precursor is an intrinsic antagonist for its active growth factor

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Unprocessed BMP9 precursor is an intrinsic antagonist for its active growth factor

BMP9, a member of the TGFβ superfamily, plays a crucial role in angiogenesis, tissue development, and innate immunity. Dysregulation of BMP9 signaling is implicated in various diseases. Unlike latent TGFβs, BMP9 is produced as a precursor that is processed into an active pro-protein complex. However, the regulatory mechanisms governing the precursor’s activity and its biological functions have been largely unexplored. In this study, we demonstrate that the unprocessed BMP9 precursor acts as an intrinsic antagonist to its pro-protein in angiogenesis and osteogenesis. This inhibition occurs through competitive binding to the receptors ENG and ALK1. We also identify structural requirements for the precursor’s recognition by these receptors. Our findings reveal previously underappreciated functions of the BMP9 precursor and its regulatory mechanisms in growth factor signaling, with significant implications for developmental biology and clinical interventions.

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来源期刊

Structure 生物-生化与分子生物学

CiteScore

8.90

自引率

1.80%

发文量

155

审稿时长

3-8 weeks

期刊介绍： Structure aims to publish papers of exceptional interest in the field of structural biology. The journal strives to be essential reading for structural biologists, as well as biologists and biochemists that are interested in macromolecular structure and function. Structure strongly encourages the submission of manuscripts that present structural and molecular insights into biological function and mechanism. Other reports that address fundamental questions in structural biology, such as structure-based examinations of protein evolution, folding, and/or design, will also be considered. We will consider the application of any method, experimental or computational, at high or low resolution, to conduct structural investigations, as long as the method is appropriate for the biological, functional, and mechanistic question(s) being addressed. Likewise, reports describing single-molecule analysis of biological mechanisms are welcome. In general, the editors encourage submission of experimental structural studies that are enriched by an analysis of structure-activity relationships and will not consider studies that solely report structural information unless the structure or analysis is of exceptional and broad interest. Studies reporting only homology models, de novo models, or molecular dynamics simulations are also discouraged unless the models are informed by or validated by novel experimental data; rationalization of a large body of existing experimental evidence and making testable predictions based on a model or simulation is often not considered sufficient.