2qcq
From Proteopedia
(New page: 200px<br /> <applet load="2qcq" size="450" color="white" frame="true" align="right" spinBox="true" caption="2qcq, resolution 2.21Å" /> '''Crystal structure o...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2qcq. | + | [[Image:2qcq.jpg|left|200px]]<br /><applet load="2qcq" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2qcq" size=" | + | |
caption="2qcq, resolution 2.21Å" /> | caption="2qcq, resolution 2.21Å" /> | ||
'''Crystal structure of Bone Morphogenetic Protein-3 (BMP-3)'''<br /> | '''Crystal structure of Bone Morphogenetic Protein-3 (BMP-3)'''<br /> | ||
| Line 8: | Line 7: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2QCQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 2QCQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QCQ OCA]. |
==Reference== | ==Reference== | ||
| Line 19: | Line 18: | ||
[[Category: tgf-beta]] | [[Category: tgf-beta]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:34:35 2008'' |
Revision as of 10:34, 23 January 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 muM 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):12238-12247. Epub 2007 Oct 9. PMID:17924656
Page seeded by OCA on Wed Jan 23 12:34:35 2008
