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2qcq
From Proteopedia
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[[Image:2qcq.jpg|left|200px]] | [[Image:2qcq.jpg|left|200px]] | ||
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'''Crystal structure of Bone Morphogenetic Protein-3 (BMP-3)''' | '''Crystal structure of Bone Morphogenetic Protein-3 (BMP-3)''' | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Allendorph, G P.]] | [[Category: Allendorph, G P.]] | ||
| - | [[Category: | + | [[Category: Bmp]] |
| - | [[Category: | + | [[Category: Signaling protein]] |
| - | [[Category: | + | [[Category: Tgf-beta]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 14:44:19 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 11:44, 4 May 2008
Crystal structure of Bone Morphogenetic Protein-3 (BMP-3)
Overview
Bone morphogenetic proteins (BMPs) are extracellular messenger ligands involved in controlling a wide array of developmental and intercellular signaling processes. To initiate their specific intracellular signaling pathways, the ligands recognize and bind two structurally related serine/threonine kinase receptors, termed type I and type II, on the cell surface. Here, we present the crystal structures of BMP-3 and BMP-6, of which BMP-3 has remained poorly understood with respect to its receptor identity, affinity, and specificity. Using surface plasmon resonance (BIAcore) we show that BMP-3 binds Activin Receptor type II (ActRII) with Kd approximately 1.8 microM but ActRIIb with 30-fold higher affinity at Kd approximately 53 nM. This low affinity for ActRII may involve Ser-28 and Asp-33 of BMP-3, which are found only in BMP-3's type II receptor-binding interfaces. Point mutations of either residue to alanine results in up to 20-fold higher affinity to either receptor. We further demonstrate by Smad-based whole cell luciferase assays that the increased affinity of BMP-3S28A to ActRII enables the ligand's signaling ability to a level comparable to that of BMP-6. Focusing on BMP-3's preference for ActRIIb, we find that Lys-76 of ActRII and the structurally equivalent Glu-76 of ActRIIb are distinct between the two receptors. We demonstrate that ActRIIbE76K and ActRII bind BMP-3 with similar affinity, indicating BMP-3 receptor specificity is controlled by the interaction of Lys-30 of BMP-3 with Glu-76 of ActRIIb. These studies illustrate how a single amino acid can regulate the specificity of ligand-receptor binding and potentially alter biological signaling and function in vivo.
About this Structure
2QCQ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
BMP-3 and BMP-6 structures illuminate the nature of binding specificity with receptors., Allendorph GP, Isaacs MJ, Kawakami Y, Belmonte JC, Choe S, Biochemistry. 2007 Oct 30;46(43):12238-47. Epub 2007 Oct 9. PMID:17924656 Page seeded by OCA on Sun May 4 14:44:19 2008
