The Solution Structure of BMPR-IA Reveals a Local Disorder-to-Order Transition upon BMP-2 Binding
The Solution Structure of BMPR-IA Reveals a Local Disorder-to-Order Transition upon BMP-2 Binding
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DOI：
10.1021/bi801059j
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发表时间：
2008-11-18
期刊：
影响因子：
2.9
通讯作者：
Kessler, Horst
中科院分区：
文献类型：
--
作者：
Klages, Jochen;Kotzsch, Alexander;Kessler, Horst
BMP受体IA的细胞外结构域的结构在溶液中通过NMR光谱测定，并与其与其配体BMP-2结合时的结构进行比较。虽然二级结构的大部分在结合和未结合形式之间是高度保守的，但在BMPR-IA的β 4 β 5环中可以观察到大的构象重排，其与BMP-2接触并含有BMPR-IA-BMP-2相互作用的主要结合决定簇。在其未结合形式中，BMPR-IA中的螺旋α 1缺失，其位于BMP-2的结合表位的中心。由于BMP-2在与BMPR-IA结合时也显示I型受体表位的构象变化，因此两种结合配偶体都通过诱导配合机制以使其结合界面适应给定的相互作用表面。这两个合作伙伴的固有灵活性可能解释了混杂的BMP蛋白超家族中观察到的配体-受体相互作用。
The structure of the extracellular domain of BMP receptor IA was determined in solution by NMR spectroscopy and compared to its structure when bound to its ligand BMP-2. While most parts of the secondary structure are highly conserved between the bound and unbound forms, large conformational rearrangements can be observed in the beta 4 beta 5 loop of BMPR-IA, which is in contact with BMP-2 and harbors the main binding determinants for the BMPR-IA-BMP-2 interaction. In its unbound form, helix alpha 1 in BMPR-IA, which is in the center of the binding epitope for BMP-2, is missing. Since BMP-2 also shows conformational changes in the type I receptor epitope upon binding to BMPR-IA, both binding partners pass through an induced fit mechanism to adapt their binding interfaces to a given interaction surface. The inherent fiexibility of both partners possibly explains the promiscuous ligand-receptor interaction observed in the BMP protein superfamily.