7V6Y

Cryo-EM structure of Patched in lipid nanodisc - the wildtype, 3.5 angstrom (re-processed with dataset of 7dzq)

Replaces:  7DZQ

Summary for 7V6Y

• Entry DOI: 10.2210/pdb7v6y/pdb
• EMDB information: 31753
• Descriptor: Protein patched homolog 1,Protein patched homolog 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, CHOLESTEROL, ... (5 entities in total)
• Functional Keywords: caveolae, hedgehog signaling, lipid nanodisc, patched, ptc1 dimer, membrane protein
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 1
• Total formula weight: 123980.42

Authors

Luo, Y.,Zhao, Y.,Qu, Q.,Li, D. (deposition date: 2021-08-20, release date: 2021-09-22, Last modification date: 2025-03-19)

Primary citation

Luo, Y.,Wan, G.,Zhang, X.,Zhou, X.,Wang, Q.,Fan, J.,Cai, H.,Ma, L.,Wu, H.,Qu, Q.,Cong, Y.,Zhao, Y.,Li, D.
Cryo-EM study of patched in lipid nanodisc suggests a structural basis for its clustering in caveolae.
Structure, 29:1286-, 2021

PubMed Abstract: The 12-transmembrane protein Patched (Ptc1) acts as a suppressor for Hedgehog (Hh) signaling by depleting sterols in the cytoplasmic membrane leaflet that are required for the activation of downstream regulators. The positive modulator Hh inhibits Ptc1's transporter function by binding to Ptc1 and its co-receptors, which are locally concentrated in invaginated microdomains known as caveolae. Here, we reconstitute the mouse Ptc1 into lipid nanodiscs and determine its structure using single-particle cryoelectron microscopy. The structure is overall similar to those in amphipol and detergents but displays various conformational differences in the transmembrane region. Although most particles show monomers, we observe Ptc1 dimers with distinct interaction patterns and different membrane curvatures, some of which are reminiscent of caveolae. We find that an extramembranous "hand-shake" region rich in hydrophobic and aromatic residues mediates inter-Ptc1 interactions under different membrane curvatures. Our data provide a plausible framework for Ptc1 clustering in the highly curved caveolae.

PubMed: 34174188
DOI: 10.1016/j.str.2021.06.004

Experimental method

ELECTRON MICROSCOPY (3.5 Å)