Structural mechanism for sterol sensing and transport by OSBP-related proteins

Young Jun Im, Sumana Raychaudhuri, William A. Prinz and James H. Hurley ()
Additional contact information
Young Jun Im: Laboratory of Molecular Biology
Sumana Raychaudhuri: National Institutes of Health, US Department of Health and Human Services
William A. Prinz: National Institutes of Health, US Department of Health and Human Services
James H. Hurley: Laboratory of Molecular Biology

Nature, 2005, vol. 437, issue 7055, 154-158

Abstract: Abstract The oxysterol-binding-protein (OSBP)-related proteins (ORPs) are conserved from yeast to humans1,2, and are implicated in the regulation of sterol homeostasis3,4 and in signal transduction pathways5. Here we report the structure of the full-length yeast ORP Osh4 (also known as Kes1) at 1.5–1.9 Å resolution in complexes with ergosterol, cholesterol, and 7-, 20- and 25-hydroxycholesterol. We find that a single sterol molecule binds within a hydrophobic tunnel in a manner consistent with a transport function for ORPs. The entrance is blocked by a flexible amino-terminal lid and surrounded by basic residues that are critical for Osh4 function. The structure of the open state of a lid-truncated form of Osh4 was determined at 2.5 Å resolution. Structural analysis and limited proteolysis show that sterol binding closes the lid and stabilizes a conformation favouring transport across aqueous barriers and signal transmission. The structure of Osh4 in the absence of ligand exposes potential phospholipid-binding sites that are positioned for membrane docking and sterol exchange. On the basis of these observations, we propose a model in which sterol and membrane binding promote reciprocal conformational changes that facilitate a sterol transfer and signalling cycle.

Date: 2005
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature03923 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:437:y:2005:i:7055:d:10.1038_nature03923

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature03923

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().