3n1m

From Proteopedia

(Difference between revisions)

Revision as of 06:56, 5 August 2016

Crystal Structure of IhhN bound to BOCFn3

Structural highlights

3n1m is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3d1m, 3n1f, 3n1g, 3n1o, 3n1p, 3n1q, 3n1r
Gene:	IHH (HUMAN), BOC, UNQ604/PRO1190 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[IHH_HUMAN] Brachydactyly type A1;Acrocapitofemoral dysplasia. Defects in IHH are the cause of brachydactyly type A1 (BDA1) [MIM:112500]. BDA1 is an autosomal dominant disorder characterized by middle phalanges of all the digits rudimentary or fused with the terminal phalanges. The proximal phalanges of the thumbs and big toes are short.^[1] ^[2] Defects in IHH are a cause of acrocapitofemoral dysplasia (ACFD) [MIM:607778]. ACFD is a disorder characterized by short stature of variable severity with postnatal onset. The most constant radiographic abnormalities are observed in the tubular bones of the hands and in the proximal part of the femur. Cone-shaped epiphyses or a similar epiphyseal configuration with premature epimetaphyseal fusion result in shortening of the skeletal components involved. Cone-shaped epiphyses were also present to a variable extent at the shoulders, knees, and ankles.^[3]

Function

[IHH_HUMAN] Intercellular signal essential for a variety of patterning events during development. Binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes. Implicated in endochondral ossification: may regulate the balance between growth and ossification of the developing bones. Induces the expression of parathyroid hormone-related protein (PTHRP) (By similarity). [BOC_HUMAN] Component of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells. Promotes differentiation of myogenic cells.

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

Hedgehog (Hh) signaling proteins stimulate cell proliferation, differentiation, and tissue patterning at multiple points in animal development. A single Hh homolog is present in Drosophila, but three Hh homologs, Sonic Hh, Indian Hh, and Desert Hh, are present in mammals. Distribution, movement, and reception of Hh signals are tightly regulated, and abnormal Hh signaling is associated with developmental defects and cancer. In addition to the integral membrane proteins Patched and Smoothened, members of the Drosophila Ihog family of adhesion-like molecules have recently been shown to bind Hh proteins with micromolar affinity and positively regulate Hh signaling. Cell adhesion molecule-related, down-regulated by oncogenes (CDO) and Brother of CDO (BOC) are the closest mammalian relatives of Drosophila Ihog, and CDO binds Sonic Hh with micromolar affinity and positively regulates Hh signaling. Despite these similarities, structural and biochemical studies have shown that Ihog and CDO utilize nonorthologous domains and completely different binding modes to interact with cognate Hh proteins. We report here biochemical and x-ray structural studies of Sonic, Indian, and Desert Hh proteins both alone and complexed with active domains of CDO and BOC. These results show that all mammalian Hh proteins bind CDO and BOC in the same manner. We also show that interactions between Hh proteins and CDO are weakened at low pH. Formation of Hh-mediated Hh oligomers is thought to be an important feature of normal Hh signaling, but no conserved self-interaction between Hh proteins is apparent from inspection of 14 independent Hh-containing crystal lattices.

All mammalian Hedgehog proteins interact with cell adhesion molecule, down-regulated by oncogenes (CDO) and brother of CDO (BOC) in a conserved manner.,Kavran JM, Ward MD, Oladosu OO, Mulepati S, Leahy DJ J Biol Chem. 2010 Aug 6;285(32):24584-90. Epub 2010 Jun 1. PMID:20519495^[4]

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

References

↑ Gao B, Guo J, She C, Shu A, Yang M, Tan Z, Yang X, Guo S, Feng G, He L. Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1. Nat Genet. 2001 Aug;28(4):386-8. PMID:11455389 doi:http://dx.doi.org/10.1038/ng577
↑ McCready ME, Sweeney E, Fryer AE, Donnai D, Baig A, Racacho L, Warman ML, Hunter AG, Bulman DE. A novel mutation in the IHH gene causes brachydactyly type A1: a 95-year-old mystery resolved. Hum Genet. 2002 Oct;111(4-5):368-75. Epub 2002 Sep 7. PMID:12384778 doi:http://dx.doi.org/10.1007/s00439-002-0815-2
↑ Hellemans J, Coucke PJ, Giedion A, De Paepe A, Kramer P, Beemer F, Mortier GR. Homozygous mutations in IHH cause acrocapitofemoral dysplasia, an autosomal recessive disorder with cone-shaped epiphyses in hands and hips. Am J Hum Genet. 2003 Apr;72(4):1040-6. Epub 2003 Mar 11. PMID:12632327
↑ Kavran JM, Ward MD, Oladosu OO, Mulepati S, Leahy DJ. All mammalian Hedgehog proteins interact with cell adhesion molecule, down-regulated by oncogenes (CDO) and brother of CDO (BOC) in a conserved manner. J Biol Chem. 2010 Aug 6;285(32):24584-90. Epub 2010 Jun 1. PMID:20519495 doi:10.1074/jbc.M110.131680

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3n1m"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of IhhN bound to BOCFn3==
 <StructureSection load='3n1m' size='340' side='right' caption='[[3n1m]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3n1m]] is a 2 chain structure with 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=3N1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N1M FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3n1m]] 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=3N1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N1M FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3d1m|3d1m]], [[3n1f|3n1f]], [[3n1g|3n1g]], [[3n1o|3n1o]], [[3n1p|3n1p]], [[3n1q|3n1q]], [[3n1r|3n1r]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IHH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), BOC, UNQ604/PRO1190 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IHH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BOC, UNQ604/PRO1190 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3n1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n1m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3n1m RCSB], [http://www.ebi.ac.uk/pdbsum/3n1m 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=3n1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n1m OCA], [http://pdbe.org/3n1m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3n1m RCSB], [http://www.ebi.ac.uk/pdbsum/3n1m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3n1m ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/IHH_HUMAN IHH_HUMAN]] Brachydactyly type A1;Acrocapitofemoral dysplasia. Defects in IHH are the cause of brachydactyly type A1 (BDA1) [MIM:[http://omim.org/entry/112500 112500]]. BDA1 is an autosomal dominant disorder characterized by middle phalanges of all the digits rudimentary or fused with the terminal phalanges. The proximal phalanges of the thumbs and big toes are short.<ref>PMID:11455389</ref> <ref>PMID:12384778</ref>   Defects in IHH are a cause of acrocapitofemoral dysplasia (ACFD) [MIM:[http://omim.org/entry/607778 607778]]. ACFD is a disorder characterized by short stature of variable severity with postnatal onset. The most constant radiographic abnormalities are observed in the tubular bones of the hands and in the proximal part of the femur. Cone-shaped epiphyses or a similar epiphyseal configuration with premature epimetaphyseal fusion result in shortening of the skeletal components involved. Cone-shaped epiphyses were also present to a variable extent at the shoulders, knees, and ankles.<ref>PMID:12632327</ref>
+== Function ==
+[[http://www.uniprot.org/uniprot/IHH_HUMAN IHH_HUMAN]] Intercellular signal essential for a variety of patterning events during development. Binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes. Implicated in endochondral ossification: may regulate the balance between growth and ossification of the developing bones. Induces the expression of parathyroid hormone-related protein (PTHRP) (By similarity). [[http://www.uniprot.org/uniprot/BOC_HUMAN BOC_HUMAN]] Component of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells. Promotes differentiation of myogenic cells.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 16: / Line 21: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3n1m ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 26: / Line 31: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3n1m" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Kavran, J M]]
 [[Category: Leahy, D J]]

3n1m

From Proteopedia

Revision as of 06:56, 5 August 2016

Crystal Structure of IhhN bound to BOCFn3

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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