The Solution Structure of BMPR-IA Reveals a Local Disorder-to-Order Transition upon BMP-2 Binding

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• 作者：Jochen Klages ; Alexander Kotzsch ; Murray Coles ; Walter Sebald ; Joachim Nickel ; Thomas Mü ; ller ; Horst Kessler
• 刊名：Biochemistry
• 出版年：2008
• 出版时间：November 18, 2008
• 年：2008
• 卷：47
• 期：46
• 页码：11930-11939
• 全文大小：413K
• 年卷期：v.47,no.46(November 18, 2008)
• ISSN：1520-4995

文摘

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 β4β5 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 α1 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 flexibility of both partners possibly explains the promiscuous ligand−receptor interaction observed in the BMP protein superfamily.