Structural Basis for Cholesterol Transport-like Activity of the Hedgehog Receptor Patched.

Cell
Yunxiao ZhangPhilip A Beachy

Abstract

Hedgehog protein signals mediate tissue patterning and maintenance by binding to and inactivating their common receptor Patched, a 12-transmembrane protein that otherwise would suppress the activity of the 7-transmembrane protein Smoothened. Loss of Patched function, the most common cause of basal cell carcinoma, permits unregulated activation of Smoothened and of the Hedgehog pathway. A cryo-EM structure of the Patched protein reveals striking transmembrane domain similarities to prokaryotic RND transporters. A central hydrophobic conduit with cholesterol-like contents courses through the extracellular domain and resembles that used by other RND proteins to transport substrates, suggesting Patched activity in cholesterol transport. Cholesterol activity in the inner leaflet of the plasma membrane is reduced by PTCH1 expression but rapidly restored by Hedgehog stimulation, suggesting that PTCH1 regulates Smoothened by controlling cholesterol availability.

Citations

Feb 3, 2019·The Journal of Biological Chemistry·Suzanne R Pfeffer
Apr 28, 2019·Cells·Natalia A Riobo-Del GaldoEva V Wertheimer
Dec 22, 2019·Journal of Clinical Medicine·Jorge L Rodriguez-GilWilliam J Pavan
Sep 27, 2019·Science Advances·Chao QiVolodymyr M Korkhov
Feb 23, 2020·Wiley Interdisciplinary Reviews. Developmental Biology·Eduardo D Gigante, Tamara Caspary
Jan 8, 2020·Journal of Lipid Research·Mustafa YalcinkayaArnold von Eckardstein
Jan 11, 2020·Nature Communications·Tao LongXiaochun Li
May 28, 2019·Nature Communications·Hongwu QianXin Gong
Mar 30, 2019·Basic & Clinical Pharmacology & Toxicology·Gunnar Schulte, Paweł Kozielewicz
Jul 3, 2019·Nature·Ishan DeshpandeAashish Manglik
Sep 25, 2019·Nature Chemical Biology·Amalie F RudolfChristian Siebold
Sep 16, 2020·Traffic·Yvonne Lange, Theodore L Steck
Feb 9, 2019·Nature Reviews. Nephrology·Zeinab AnvarianSøren Tvorup Christensen
Jun 5, 2020·Science Advances·Fabien CannacVolodymyr M Korkhov
Apr 18, 2019·Cancers·Elisabeth PeerFritz Aberger
Apr 6, 2019·Nature Reviews. Molecular Cell Biology·Maxence V Nachury, David U Mick
Nov 25, 2019·Traffic·Akihiro KusumiKenichi G N Suzuki
Dec 24, 2019·National Science Review·Jean-Paul Armache, Yifan Cheng
Oct 9, 2019·Molecular Pharmacology·Pawel KozielewiczGunnar Schulte
Aug 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Diana S GestoSérgio F Sousa
Sep 16, 2020·Nature Chemical Biology·Xiaofeng QiXiaochun Li
May 17, 2019·Development·Jennifer H KongRajat Rohatgi
Feb 1, 2020·The Journal of Physiology·Aichurok Kamalova, Terunaga Nakagawa
Mar 3, 2020·Nanoscale Horizons : the Home for Rapid Reports of Exceptional Significance in Nanoscience and Nanotechnolgy·Qiang WuHongda Wang
Jul 11, 2020·Life Science Alliance·Hongwen ChenXiaochun Li
May 13, 2020·Journal of Cell Science·Albert PolRobert G Parton
Jul 3, 2020·Frontiers in Chemistry·Taikangxiang YunYing Liu
Oct 7, 2020·The EMBO Journal·Stephanie SpannlSuzanne Eaton
Oct 18, 2020·International Journal of Molecular Sciences·Shoko OnoderaToshifumi Azuma
Jun 17, 2020·Seminars in Cell & Developmental Biology·Daniel KopinkeSaikat Mukhopadhyay
Sep 24, 2019·Cell·Mikael B L WinklerBjørn Panyella Pedersen
Jan 28, 2021·International Journal of Molecular Sciences·Natalie Geyer, Marco Gerling
Feb 2, 2021·Physical Chemistry Chemical Physics : PCCP·Sandra KovachkaPaolo Ruggerone
Nov 18, 2020·Nature Chemical Biology·Dror S Chorev, Carol V Robinson
Nov 18, 2020·Nature Chemical Biology·Arun RadhakrishnanChristian Siebold

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell eTOC

Cell is a scientific journal publishing research across a broad range of disciplines within the life sciences field. Discover the latest research from Cell here.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Carcinoma, Basal Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.