Molecular recognition of BMP-2 and BMP receptor IA

被引:184
作者
Keller, S [1 ]
Nickel, J [1 ]
Zhang, JL [1 ]
Sebald, W [1 ]
Mueller, TD [1 ]
机构
[1] Univ Wurzburg, Theodor Boveri Inst Biowissensch, Biozentrum, Lehrstuhl Physiol Chem 2, D-97074 Wurzburg, Germany
关键词
D O I
10.1038/nsmb756
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bone morphogenetic protein-2 (BMP-2) and other members of the TGF-beta superfamily regulate the development, maintenance and regeneration of tissues and organs. Binding epitopes for these extracellular signaling proteins have been defined, but hot spots specifying binding affinity and specificity have so far not been identified. In this study, mutational and structural analyses show that epitopes of BMP-2 and the BRIA receptor form a new type of protein-protein interface. The main chain atoms of Leu 51 and Asp53 of BMP-2 represent a hot spot of binding to BRIA. The BMP-2 variant L51P was deficient in type I receptor binding only, whereas its overall structure and its binding to type II receptors and modulator proteins, such as noggin, were unchanged. Thus, the L51P substitution converts BMP-2 into a receptor-inactive inhibitor of noggin. These results are relevant for other proteins of the TGF-beta superfamily and provide useful clues for structure-based drug design.
引用
收藏
页码:481 / 488
页数:8
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