6N7K

Cryo-EM structure of tetrameric Ptch1 in complex with ShhNp (form II)

6N7K の概要

• エントリーDOI: 10.2210/pdb6n7k/pdb
• EMDBエントリー: 0358
• 分子名称: Protein patched homolog 1, Sonic hedgehog protein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 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); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 650738.67

構造登録者

Yan, N.,Gong, X.,Qian, H.W. (登録日: 2018-11-27, 公開日: 2019-05-29, 最終更新日: 2025-05-28)

主引用文献

Qian, H.,Cao, P.,Hu, M.,Gao, S.,Yan, N.,Gong, X.
Inhibition of tetrameric Patched1 by Sonic Hedgehog through an asymmetric paradigm.
Nat Commun, 10:2320-2320, 2019

PubMed Abstract: The Hedgehog (Hh) pathway controls embryonic development and postnatal tissue maintenance and regeneration. Inhibition of Hh receptor Patched (Ptch) by the Hh ligands relieves suppression of signaling cascades. Here, we report the cryo-EM structure of tetrameric Ptch1 in complex with the palmitoylated N-terminal signaling domain of human Sonic hedgehog (ShhN) at a 4:2 stoichiometric ratio. The structure shows that four Ptch1 protomers are organized as a loose dimer of dimers. Each dimer binds to one ShhN through two distinct inhibitory interfaces, one mainly through the N-terminal peptide and the palmitoyl moiety of ShhN and the other through the Ca-mediated interface on ShhN. Map comparison reveals that the cholesteryl moiety of native ShhN occupies a recently identified extracellular steroid binding pocket in Ptch1. Our structure elucidates the tetrameric assembly of Ptch1 and suggests an asymmetric mode of action of the Hh ligands for inhibiting the potential cholesterol transport activity of Ptch1.

PubMed: 31127104
DOI: 10.1038/s41467-019-10234-9

実験手法

ELECTRON MICROSCOPY (6.5 Å)