View source for 1at0


==17-kDA fragment of hedgehog C-terminal autoprocessing domain==
<StructureSection load='1at0' size='340' side='right'caption='[[1at0]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1at0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AT0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AT0 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=1at0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1at0 OCA], [https://pdbe.org/1at0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1at0 RCSB], [https://www.ebi.ac.uk/pdbsum/1at0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1at0 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HH_DROME HH_DROME] Intercellular signal essential for a variety of patterning events during development. Establishes the anterior-posterior axis of the embryonic segments and patterns the larval imaginal disks. Binds to the patched (ptc) receptor, which functions in association with smoothened (smo), to activate the transcription of target genes wingless (wg), decapentaplegic (dpp) and ptc. In the absence of hh, ptc represses the constitutive signaling activity of smo through fused (fu).<ref>PMID:8166882</ref> <ref>PMID:1394430</ref> <ref>PMID:1340474</ref> <ref>PMID:11319862</ref>   The hedgehog protein N-product constitutes the active species in both local and long-range signaling, whereas the C-terminal product has no signaling activity. It acts as a morphogen, and diffuses long distances despite its lipidation. Heparan sulfate proteoglycans of the extracellular matrix play an essential role in diffusion. Lipophorin is required for diffusion, probably by acting as vehicle for its movement, explaining how it can spread over long distances despite its lipidation.<ref>PMID:8166882</ref> <ref>PMID:1394430</ref> <ref>PMID:1340474</ref> <ref>PMID:11319862</ref>   The hedgehog protein C-product, which mediates the autocatalytic activity, has no signaling activity.<ref>PMID:8166882</ref> <ref>PMID:1394430</ref> <ref>PMID:1340474</ref> <ref>PMID:11319862</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/at/1at0_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <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/main_output.php?pdb_ID=1at0 ConSurf].
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== Publication Abstract from PubMed ==
The approximately 25 kDa carboxy-terminal domain of Drosophila Hedgehog protein (Hh-C) possesses an autoprocessing activity that results in an intramolecular cleavage of full-length Hedgehog protein and covalent attachment of a cholesterol moiety to the newly generated amino-terminal fragment. We have identified a 17 kDa fragment of Hh-C (Hh-C17) active in the initiation of autoprocessing and report here its crystal structure. The Hh-C17 structure comprises two homologous subdomains that appear to have arisen from tandem duplication of a primordial gene. Residues in the Hh-C17 active site have been identified, and their role in Hedgehog autoprocessing probed by site-directed mutagenesis. Aspects of sequence, structure, and reaction mechanism are conserved between Hh-C17 and the self-splicing regions of inteins, permitting reconstruction of a plausible evolutionary history of Hh-C and the inteins.

Crystal structure of a Hedgehog autoprocessing domain: homology between Hedgehog and self-splicing proteins.,Hall TM, Porter JA, Young KE, Koonin EV, Beachy PA, Leahy DJ Cell. 1997 Oct 3;91(1):85-97. PMID:9335337<ref>PMID:9335337</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1at0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Drosophila melanogaster]]
[[Category: Large Structures]]
[[Category: Beachy PA]]
[[Category: Hall TMT]]
[[Category: Koonin EV]]
[[Category: Leahy DJ]]
[[Category: Porter JA]]
[[Category: Young KE]]