2qjb: Difference between revisions

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Revision as of 19:26, 20 March 2008

File:2qjb.jpg

, resolution 2.50Å

Ligands:

Gene:

BMP2, BMP2A (Homo sapiens), BMPR1A, ACVRLK3, ALK3 (Homo sapiens)

Coordinates:

save as pdb, mmCIF, xml

Crystal structure analysis of BMP-2 in complex with BMPR-IA variant IA/IB

OverviewOverview

Bone morphogenetic proteins regulate many developmental processes during embryogenesis as well as tissue homeostasis in the adult. Signaling of BMPs is accomplished by binding to two types of serine/threonine kinase transmembrane receptors termed type I and type II. Since a large number of ligands signal through a limited number of receptors, ligand-receptor interaction in the BMP superfamily is highly promiscuous with a ligand binding to various receptors and a receptor binding many different BMP ligands. In this study we investigate the interaction of BMP-2 with its two high affinity type I receptors BMPR-IA and BMPR-IB. Interestingly, 50% of the residues in the BMP-2 binding epitope of BMPR-IA are exchanged in BMPR-IB without decrease in binding affinity or specificity for BMP-2. Our structural and functional analyses show that promiscuous binding of BMP-2 to both type I receptors is achieved by inherent backbone and sidechain flexibility as well as by variable hydration of the ligand-receptor interface enabling the BMP-2 surface to adapt to different receptor geometries. Despite the high degree of amino acid variability found between BMPR-IA and BMPR-IB, three single point missense mutations in the ectodomain of BMPR-IA found in juvenile polyposis syndrome result in inactivation of BMPR-IA. On the basis of our biochemical and biophysical analyses we can show that the mutations, which are located outside the ligand binding epitope alter the local or global fold of the receptor thereby inactivating BMPR-IA and causing a loss of the BMP-2 tumor suppressor function in colon epithelial cells.

About this StructureAbout this Structure

2QJB is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Structure analysis of BMP-2 type I receptor complexes reveals a mechanism of receptor inactivation in juvenile polyposis syndrome., Kotzsch A, Nickel J, Seher A, Heinecke K, van Geersdaele L, Herrmann T, Sebald W, Mueller TD, J Biol Chem. 2007 Dec 26;. PMID:18160401

Page seeded by OCA on Thu Mar 20 18:26:30 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2qjb.jpg|left|200px]]<br /><applet load="2qjb" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:2qjb.jpg|left|200px]]
-caption="2qjb, resolution 2.50&Aring;" />
-'''Crystal structure analysis of BMP-2 in complex with BMPR-IA variant IA/IB'''<br />
+ {{Structure
+|PDB= 2qjb |SIZE=350|CAPTION= <scene name='initialview01'>2qjb</scene>, resolution 2.50&Aring;
+|SITE=
+|LIGAND= <scene name='pdbligand=CL:CHLORIDE ION'>CL</scene>
+|ACTIVITY=
+|GENE= BMP2, BMP2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), BMPR1A, ACVRLK3, ALK3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+}}
+'''Crystal structure analysis of BMP-2 in complex with BMPR-IA variant IA/IB'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-QJB is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QJB OCA].
+QJB is a [[Protein complex]] structure of sequences 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=2QJB OCA].
 ==Reference==
-Structure analysis of BMP-2 type I receptor complexes reveals a mechanism of receptor inactivation in juvenile polyposis syndrome., Kotzsch A, Nickel J, Seher A, Heinecke K, van Geersdaele L, Herrmann T, Sebald W, Mueller TD, J Biol Chem. 2007 Dec 26;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18160401 18160401]
+Structure analysis of BMP-2 type I receptor complexes reveals a mechanism of receptor inactivation in juvenile polyposis syndrome., Kotzsch A, Nickel J, Seher A, Heinecke K, van Geersdaele L, Herrmann T, Sebald W, Mueller TD, J Biol Chem. 2007 Dec 26;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18160401 18160401]
 [[Category: Homo sapiens]]
 [[Category: Protein complex]]
@@ Line 18: / Line 27: @@
 [[Category: atp-binding]]
 [[Category: chondrogenesis]]
-[[Category: cleavage on pair of basic residues]]
+[[Category: cleavage on pair of basic residue]]
 [[Category: cytokine]]
 [[Category: cytokine/receptor complex]]
@@ Line 40: / Line 49: @@
 [[Category: transmembrane]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:39:44 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:26:30 2008''