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6dmo

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Revision as of 10:12, 18 December 2019

Cryo-EM structure of human Ptch1 with three mutations L282Q/T500F/P504L

Structural highlights

6dmo is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	PTCH1, PTCH (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 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^[2]

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

References

↑ Ma G, Yu J, Xiao Y, Chan D, Gao B, Hu J, He Y, Guo S, Zhou J, Zhang L, Gao L, Zhang W, Kang Y, Cheah KS, Feng G, Guo X, Wang Y, Zhou CZ, He L. Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels. Cell Res. 2011 Sep;21(9):1343-57. doi: 10.1038/cr.2011.76. Epub 2011 May 3. PMID:21537345 doi:http://dx.doi.org/10.1038/cr.2011.76
↑ Gong X, Qian H, Cao P, Zhao X, Zhou Q, Lei J, Yan N. Structural basis for the recognition of Sonic Hedgehog by human Patched1. Science. 2018 Jun 28. pii: science.aas8935. doi: 10.1126/science.aas8935. PMID:29954986 doi:http://dx.doi.org/10.1126/science.aas8935

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6dmo"

@@ Line 1: / Line 1: @@
 ==Cryo-EM structure of human Ptch1 with three mutations L282Q/T500F/P504L==
-<StructureSection load='6dmo' size='340' side='right' caption='[[6dmo]], [[Resolution|resolution]] 4.10&Aring;' scene=''>
+<StructureSection load='6dmo' size='340' side='right'caption='[[6dmo]], [[Resolution|resolution]] 4.10&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6dmo]] is a 1 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=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>
@@ Line 26: / Line 26: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Gong, X]]
 [[Category: Qian, H W]]

6dmo

From Proteopedia

Revision as of 10:12, 18 December 2019

Cryo-EM structure of human Ptch1 with three mutations L282Q/T500F/P504L

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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