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TitleStructural basis for the recognition of Sonic Hedgehog by human Patched1.
Journal, issue, pagesScience, Vol. 361, Issue 6402, Year 2018
Publish dateAug 10, 2018
AuthorsXin Gong / Hongwu Qian / Pingping Cao / Xin Zhao / Qiang Zhou / Jianlin Lei / Nieng Yan /
PubMed AbstractThe 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 structures of human Ptch1 ...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 structures of human Ptch1 alone and in complex with the N-terminal domain of human Sonic hedgehog (ShhN) at resolutions of 3.9 and 3.6 angstroms, respectively, as determined by cryo-electron microscopy. Ptch1 comprises two interacting extracellular domains, ECD1 and ECD2, and 12 transmembrane segments (TMs), with TMs 2 to 6 constituting the sterol-sensing domain (SSD). Two steroid-shaped densities are resolved in both structures, one enclosed by ECD1/2 and the other in the membrane-facing cavity of the 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.
External linksScience / PubMed:29954986
MethodsEM (single particle)
Resolution3.6 - 4.1 Å
Structure data

7963

6dmb

EMDB-7963, PDB-6dmb:
Cryo-EM structure of human Ptch1
Method: EM (single particle) / Resolution: 3.9 Å

7964

6dmo

EMDB-7964, PDB-6dmo:
Cryo-EM structure of human Ptch1 with three mutations L282Q/T500F/P504L
Method: EM (single particle) / Resolution: 4.1 Å

7968

6dmy

EMDB-7968, PDB-6dmy:
Cryo-EM structure of human Ptch1 and ShhN complex
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

ChemComp-SER:
SERINE

ChemComp-ZN:
Unknown entry

ChemComp-CA:
Unknown entry

Source
  • homo sapiens (human)
KeywordsPROTEIN BINDING / Receptor / RND family

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