6dmo: Difference between revisions
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The entry | ==Cryo-EM structure of human Ptch1 with three mutations L282Q/T500F/P504L== | ||
<StructureSection load='6dmo' size='340' side='right' caption='[[6dmo]], [[Resolution|resolution]] 4.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6dmo]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DMO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DMO FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=6dmo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dmo OCA], [http://pdbe.org/6dmo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dmo RCSB], [http://www.ebi.ac.uk/pdbsum/6dmo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dmo ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/PTC1_HUMAN PTC1_HUMAN]] Semilobar holoprosencephaly;Monosomy 9q22.3;Alobar holoprosencephaly;Microform holoprosencephaly;Septopreoptic holoprosencephaly;Gorlin syndrome;Lobar holoprosencephaly;Midline interhemispheric variant of holoprosencephaly. The disease may be caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/PTC1_HUMAN PTC1_HUMAN]] Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH). Associates with the smoothened protein (SMO) to transduce the hedgehog's proteins signal. Seems to have a tumor suppressor function, as inactivation of this protein is probably a necessary, if not sufficient step for tumorigenesis.<ref>PMID:21537345</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The Hedgehog (Hh) pathway involved in development and regeneration is activated by the extracellular binding of Hh to the membrane receptor Patched (Ptch). We report the cryo-EM structures of human Ptch1 alone and in complex with the N-terminal domain of human Sonic hedgehog (ShhN) at resolutions of 3.9 A and 3.6 A, respectively. Ptch1 comprises two interacting extracellular domains ECD1 and ECD2 and twelve transmembrane segments (TMs), with TMs 2-6 constituting the sterol-sensing domain (SSD). Two steroid-shaped densities are resolved in both structures, one enclosed by ECD1/2, and the other on the membrane-facing cavity of SSD. Structure-guided mutational analysis shows that interaction between ShhN and Ptch1 is steroid-dependent. The structure of a steroid binding-deficient Ptch1 mutant displays pronounced conformational rearrangements. | |||
Structural basis for the recognition of Sonic Hedgehog by human Patched1.,Gong X, Qian H, Cao P, Zhao X, Zhou Q, Lei J, Yan N Science. 2018 Jun 28. pii: science.aas8935. doi: 10.1126/science.aas8935. PMID:29954986<ref>PMID:29954986</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6dmo" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Gong, X]] | |||
[[Category: Qian, H W]] | |||
[[Category: Yan, N]] | |||
[[Category: Protein binding]] | |||
[[Category: Receptor]] | |||
[[Category: Rnd family]] | |||
Revision as of 08:44, 11 July 2018
Cryo-EM structure of human Ptch1 with three mutations L282Q/T500F/P504LCryo-EM structure of human Ptch1 with three mutations L282Q/T500F/P504L
Structural highlights
Disease[PTC1_HUMAN] Semilobar holoprosencephaly;Monosomy 9q22.3;Alobar holoprosencephaly;Microform holoprosencephaly;Septopreoptic holoprosencephaly;Gorlin syndrome;Lobar holoprosencephaly;Midline interhemispheric variant of holoprosencephaly. The disease may be caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function[PTC1_HUMAN] Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH). Associates with the smoothened protein (SMO) to transduce the hedgehog's proteins signal. Seems to have a tumor suppressor function, as inactivation of this protein is probably a necessary, if not sufficient step for tumorigenesis.[1] Publication Abstract from PubMedThe Hedgehog (Hh) pathway involved in development and regeneration is activated by the extracellular binding of Hh to the membrane receptor Patched (Ptch). We report the cryo-EM structures of human Ptch1 alone and in complex with the N-terminal domain of human Sonic hedgehog (ShhN) at resolutions of 3.9 A and 3.6 A, respectively. Ptch1 comprises two interacting extracellular domains ECD1 and ECD2 and twelve transmembrane segments (TMs), with TMs 2-6 constituting the sterol-sensing domain (SSD). Two steroid-shaped densities are resolved in both structures, one enclosed by ECD1/2, and the other on the membrane-facing cavity of SSD. Structure-guided mutational analysis shows that interaction between ShhN and Ptch1 is steroid-dependent. The structure of a steroid binding-deficient Ptch1 mutant displays pronounced conformational rearrangements. Structural basis for the recognition of Sonic Hedgehog by human Patched1.,Gong X, Qian H, Cao P, Zhao X, Zhou Q, Lei J, Yan N Science. 2018 Jun 28. pii: science.aas8935. doi: 10.1126/science.aas8935. PMID:29954986[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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