1m4u: Difference between revisions

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<StructureSection load='1m4u' size='340' side='right'caption='[[1m4u]], [[Resolution|resolution]] 2.42&Aring;' scene=''>
<StructureSection load='1m4u' size='340' side='right'caption='[[1m4u]], [[Resolution|resolution]] 2.42&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1m4u]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M4U OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1M4U FirstGlance]. <br>
<table><tr><td colspan='2'>[[1m4u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M4U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M4U FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.42&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1bmp|1bmp]], [[3bmp|3bmp]], [[1es7|1es7]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BMP7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NOG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1m4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m4u OCA], [https://pdbe.org/1m4u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m4u RCSB], [https://www.ebi.ac.uk/pdbsum/1m4u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m4u ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1m4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m4u OCA], [http://pdbe.org/1m4u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1m4u RCSB], [http://www.ebi.ac.uk/pdbsum/1m4u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1m4u ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/NOGG_HUMAN NOGG_HUMAN]] Defects in NOG are a cause of symphalangism proximal syndrome (SYM1) [MIM:[http://omim.org/entry/185800 185800]]. SYM1 is characterized by the hereditary absence of the proximal interphalangeal (PIP) joints (Cushing symphalangism). Severity of PIP joint involvement diminishes towards the radial side. Distal interphalangeal joints are less frequently involved and metacarpophalangeal joints are rarely affected whereas carpal bone malformation and fusion are common. In the lower extremities, tarsal bone coalition is common. Conducive hearing loss is seen and is due to fusion of the stapes to the petrous part of the temporal bone.<ref>PMID:10080184</ref> <ref>PMID:11846737</ref> <ref>PMID:11857750</ref> <ref>PMID:15770128</ref>  Defects in NOG are the cause of multiple synostoses syndrome type 1 (SYNS1) [MIM:[http://omim.org/entry/186500 186500]]; also known as synostoses, multiple, with brachydactyly/symphalangism-brachydactyly syndrome. SYNS1 is characterized by tubular-shaped (hemicylindrical) nose with lack of alar flare, otosclerotic deafness, and multiple progressive joint fusions commencing in the hand. The joint fusions are progressive, commencing in the fifth proximal interphalangeal joint in early childhood (or at birth in some individuals) and progressing in an ulnar-to-radial and proximal-to-distal direction. With increasing age, ankylosis of other joints, including the cervical vertebrae, hips, and humeroradial joints, develop.<ref>PMID:20503332</ref>  Defects in NOG are the cause of tarsal-carpal coalition syndrome (TCC) [MIM:[http://omim.org/entry/186570 186570]]. TCC is an autosomal dominant disorder characterized by fusion of the carpals, tarsals and phalanges, short first metacarpals causing brachydactyly, and humeroradial fusion. TCC is allelic to SYM1, and different mutations in NOG can result in either TCC or SYM1 in different families.<ref>PMID:11545688</ref>  Defects in NOG are a cause of stapes ankylosis with broad thumb and toes (SABTS) [MIM:[http://omim.org/entry/184460 184460]]; also known as Teunissen-Cremers syndrome. SABTS is a congenital autosomal dominant disorder that includes hyperopia, a hemicylindrical nose, broad thumbs, great toes, and other minor skeletal anomalies but lacked carpal and tarsal fusion and symphalangism.<ref>PMID:12089654</ref>  Defects in NOG are the cause of brachydactyly type B2 (BDB2) [MIM:[http://omim.org/entry/611377 611377]]. BDB2 is a subtype of brachydactyly characterized by hypoplasia/aplasia of distal phalanges in combination with distal symphalangism, fusion of carpal/tarsal bones, and partial cutaneous syndactyly.<ref>PMID:17668388</ref> 
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/BMP7_HUMAN BMP7_HUMAN]] Induces cartilage and bone formation. May be the osteoinductive factor responsible for the phenomenon of epithelial osteogenesis. Plays a role in calcium regulation and bone homeostasis. [[http://www.uniprot.org/uniprot/NOGG_HUMAN NOGG_HUMAN]] Essential for cartilage morphogenesis and joint formation. Inhibitor of bone morphogenetic proteins (BMP) signaling which is required for growth and patterning of the neural tube and somite.<ref>PMID:12478285</ref> 
[https://www.uniprot.org/uniprot/BMP7_HUMAN BMP7_HUMAN] Induces cartilage and bone formation. May be the osteoinductive factor responsible for the phenomenon of epithelial osteogenesis. Plays a role in calcium regulation and bone homeostasis.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/m4/1m4u_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/m4/1m4u_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Affolter, M]]
[[Category: Affolter M]]
[[Category: Choe, S]]
[[Category: Choe S]]
[[Category: Economides, A N]]
[[Category: Economides AN]]
[[Category: Greenwald, J]]
[[Category: Greenwald J]]
[[Category: Groppe, J]]
[[Category: Groppe J]]
[[Category: Izpisua-Belmonte, J C]]
[[Category: Izpisua-Belmonte JC]]
[[Category: Kwiatkowski, W]]
[[Category: Kwiatkowski W]]
[[Category: Rodriguez-Leon, J]]
[[Category: Rodriguez-Leon J]]
[[Category: Vale, W W]]
[[Category: Vale WW]]
[[Category: Wiater, E]]
[[Category: Wiater E]]
[[Category: Bmp antagonist]]
[[Category: Bmp-7]]
[[Category: Bone morphogenetic protein]]
[[Category: Cystine knot]]
[[Category: Hormone-growth factor complex]]
[[Category: Noggin]]

Latest revision as of 10:00, 30 October 2024

Crystal structure of Bone Morphogenetic Protein-7 (BMP-7) in complex with the secreted antagonist NogginCrystal structure of Bone Morphogenetic Protein-7 (BMP-7) in complex with the secreted antagonist Noggin

Structural highlights

1m4u is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.42Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BMP7_HUMAN Induces cartilage and bone formation. May be the osteoinductive factor responsible for the phenomenon of epithelial osteogenesis. Plays a role in calcium regulation and bone homeostasis.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The interplay between bone morphogenetic proteins (BMPs) and their antagonists governs developmental and cellular processes as diverse as establishment of the embryonic dorsal-ventral axis, induction of neural tissue, formation of joints in the skeletal system and neurogenesis in the adult brain. So far, the three-dimensional structures of BMP antagonists and the structural basis for inactivation have remained unknown. Here we report the crystal structure of the antagonist Noggin bound to BMP-7, which shows that Noggin inhibits BMP signalling by blocking the molecular interfaces of the binding epitopes for both type I and type II receptors. The BMP-7-binding affinity of site-specific variants of Noggin is correlated with alterations in bone formation and apoptosis in chick limb development, showing that Noggin functions by sequestering its ligand in an inactive complex. The scaffold of Noggin contains a cystine (the oxidized form of cysteine) knot topology similar to that of BMPs; thus, ligand and antagonist seem to have evolved from a common ancestral gene.

Structural basis of BMP signalling inhibition by the cystine knot protein Noggin.,Groppe J, Greenwald J, Wiater E, Rodriguez-Leon J, Economides AN, Kwiatkowski W, Affolter M, Vale WW, Belmonte JC, Choe S Nature. 2002 Dec 12;420(6916):636-42. PMID:12478285[1]

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

See Also

References

  1. ↑ Groppe J, Greenwald J, Wiater E, Rodriguez-Leon J, Economides AN, Kwiatkowski W, Affolter M, Vale WW, Belmonte JC, Choe S. Structural basis of BMP signalling inhibition by the cystine knot protein Noggin. Nature. 2002 Dec 12;420(6916):636-42. PMID:12478285 doi:10.1038/nature01245

1m4u, resolution 2.42Å

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