4uhy

From Proteopedia

(Difference between revisions)

Revision as of 11:47, 15 December 2016

Crystal structure of the human RGMA-BMP2 complex

Structural highlights

4uhy is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4uhz, 4ui0, 4ui1, 4ui2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[BMP2_HUMAN] Induces cartilage and bone formation. [RGMA_HUMAN] Member of the repulsive guidance molecule (RGM) family that performs several functions in the developing and adult nervous system. Regulates cephalic neural tube closure, inhibits neurite outgrowth and cortical neuron branching, and the formation of mature synapses. Binding to its receptor NEO1/neogenin induces activation of RHOA-ROCK1/Rho-kinase signaling pathway through UNC5B-ARHGEF12/LARG-PTK2/FAK1 cascade, leading to collapse of the neuronal growth cone and neurite outgrowth inhibition. Furthermore, RGMA binding to NEO1/neogenin leads to HRAS inactivation by influencing HRAS-PTK2/FAK1-AKT1 pathway. It also functions as a bone morphogenetic protein (BMP) coreceptor that may signal through SMAD1, SMAD5, and SMAD8.^[1] ^[2]

Publication Abstract from PubMed

Repulsive guidance molecules (RGMs) control crucial processes including cell motility, adhesion, immune-cell regulation and systemic iron metabolism. RGMs signal via the neogenin (NEO1) and the bone morphogenetic protein (BMP) pathways. Here, we report crystal structures of the N-terminal domains of all human RGM family members in complex with the BMP ligand BMP2, revealing a new protein fold and a conserved BMP-binding mode. Our structural and functional data suggest a pH-linked mechanism for RGM-activated BMP signaling and offer a rationale for RGM mutations causing juvenile hemochromatosis. We also determined the crystal structure of the ternary BMP2-RGM-NEO1 complex, which, along with solution scattering and live-cell super-resolution fluorescence microscopy, indicates BMP-induced clustering of the RGM-NEO1 complex. Our results show how RGM acts as the central hub that links BMP and NEO1 and physically connects these fundamental signaling pathways.

Repulsive guidance molecule is a structural bridge between neogenin and bone morphogenetic protein.,Healey EG, Bishop B, Elegheert J, Bell CH, Padilla-Parra S, Siebold C Nat Struct Mol Biol. 2015 May 4. doi: 10.1038/nsmb.3016. PMID:25938661^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hata K, Kaibuchi K, Inagaki S, Yamashita T. Unc5B associates with LARG to mediate the action of repulsive guidance molecule. J Cell Biol. 2009 Mar 9;184(5):737-50. doi: 10.1083/jcb.200807029. PMID:19273616 doi:http://dx.doi.org/10.1083/jcb.200807029
↑ Endo M, Yamashita T. Inactivation of Ras by p120GAP via focal adhesion kinase dephosphorylation mediates RGMa-induced growth cone collapse. J Neurosci. 2009 May 20;29(20):6649-62. doi: 10.1523/JNEUROSCI.0927-09.2009. PMID:19458235 doi:http://dx.doi.org/10.1523/JNEUROSCI.0927-09.2009
↑ Healey EG, Bishop B, Elegheert J, Bell CH, Padilla-Parra S, Siebold C. Repulsive guidance molecule is a structural bridge between neogenin and bone morphogenetic protein. Nat Struct Mol Biol. 2015 May 4. doi: 10.1038/nsmb.3016. PMID:25938661 doi:http://dx.doi.org/10.1038/nsmb.3016

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4uhy"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the human RGMA-BMP2 complex==
 <StructureSection load='4uhy' size='340' side='right' caption='[[4uhy]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4uhy]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UHY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UHY FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4uhz|4uhz]], [[4ui0|4ui0]], [[4ui1|4ui1]], [[4ui2|4ui2]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4uhy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uhy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4uhy RCSB], [http://www.ebi.ac.uk/pdbsum/4uhy PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4uhy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uhy OCA], [http://pdbe.org/4uhy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uhy RCSB], [http://www.ebi.ac.uk/pdbsum/4uhy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4uhy ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4uhy" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Bone morphogenetic protein|Bone morphogenetic protein]]
 == References ==
 <references/>
@@ Line 24: / Line 29: @@
 [[Category: Elegheert, J]]
 [[Category: Healey, E G]]
-[[Category: Parra, S Padilla-]]
+[[Category: Padilla-Parra, S]]
 [[Category: Siebold, C]]
 [[Category: Axon guidance]]

4uhy

From Proteopedia

Revision as of 11:47, 15 December 2016

Crystal structure of the human RGMA-BMP2 complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox