6DMO

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

6DMO の概要

• エントリーDOI: 10.2210/pdb6dmo/pdb
• EMDBエントリー: 7964
• 分子名称: Protein patched homolog 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: receptor, rnd family, protein binding
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 151797.10

構造登録者

Yan, N.,Gong, X.,Qian, H.W. (登録日: 2018-06-05, 公開日: 2018-07-11, 最終更新日: 2025-05-14)

主引用文献

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, 361:-, 2018

PubMed Abstract: 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.

PubMed: 29954986
DOI: 10.1126/science.aas8935

実験手法

ELECTRON MICROSCOPY (4.1 Å)