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骨形态发生蛋白(BMP)配体与信号传导的结构视角

Structural perspective of BMP ligands and signaling.

作者信息

Gipson Gregory R, Goebel Erich J, Hart Kaitlin N, Kappes Emily C, Kattamuri Chandramohan, McCoy Jason C, Thompson Thomas B

机构信息

Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Medical Sciences Building, Cincinnati, OH 45267, USA.

Department of Pharmacology and Systems Physiology, University of Cincinnati, Medical Sciences Building, Cincinnati, OH 45267, USA.

出版信息

Bone. 2020 Nov;140:115549. doi: 10.1016/j.bone.2020.115549. Epub 2020 Jul 27.

Abstract

The Bone Morphogenetic Proteins (BMPs) are the largest class signaling molecules within the greater Transforming Growth Factor Beta (TGFβ) family, and are responsible for a wide array of biological functions, including dorsal-ventral patterning, skeletal development and maintenance, as well as cell homeostasis. As such, dysregulation of BMPs results in a number of diseases, including fibrodysplasia ossificans progressiva (FOP) and pulmonary arterial hypertension (PAH). Therefore, understanding BMP signaling and regulation at the molecular level is essential for targeted therapeutic intervention. This review discusses the recent advances in the structural and biochemical characterization of BMPs, from canonical ligand-receptor interactions to co-receptors and antagonists. This work aims to highlight how BMPs differ from other members of the TGFβ family, and how that information can be used to further advance the field. Lastly, this review discusses several gaps in the current understanding of BMP structures, with the aim that discussion of these gaps will lead to advancements in the field.

摘要

骨形态发生蛋白(BMPs)是更大的转化生长因子β(TGFβ)家族中最大的一类信号分子,负责多种生物学功能,包括背腹模式形成、骨骼发育与维持以及细胞内稳态。因此,BMPs失调会导致多种疾病,包括进行性骨化性纤维发育不良(FOP)和肺动脉高压(PAH)。所以,在分子水平上理解BMP信号传导和调控对于靶向治疗干预至关重要。本综述讨论了BMPs在结构和生化特性方面的最新进展,从经典的配体-受体相互作用到共受体和拮抗剂。这项工作旨在突出BMPs与TGFβ家族其他成员的不同之处,以及如何利用这些信息进一步推动该领域的发展。最后,本综述讨论了当前对BMP结构理解中的几个空白,希望对这些空白的讨论能推动该领域的进步。

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