1zhy: Difference between revisions
New page: left|200px<br /><applet load="1zhy" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zhy, resolution 1.60Å" /> '''Structure of yeast o... |
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[[Image:1zhy.gif|left|200px]]<br /><applet load="1zhy" size=" | [[Image:1zhy.gif|left|200px]]<br /><applet load="1zhy" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1zhy, resolution 1.60Å" /> | caption="1zhy, resolution 1.60Å" /> | ||
'''Structure of yeast oxysterol binding protein Osh4 in complex with cholesterol'''<br /> | '''Structure of yeast oxysterol binding protein Osh4 in complex with cholesterol'''<br /> | ||
==Overview== | ==Overview== | ||
The oxysterol-binding-protein (OSBP)-related proteins (ORPs) are conserved | The oxysterol-binding-protein (OSBP)-related proteins (ORPs) are conserved from yeast to humans, and are implicated in the regulation of sterol homeostasis and in signal transduction pathways. Here we report the structure of the full-length yeast ORP Osh4 (also known as Kes1) at 1.5-1.9 A 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 A 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. | ||
==About this Structure== | ==About this Structure== | ||
1ZHY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with PB and CLR as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 1ZHY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=PB:'>PB</scene> and <scene name='pdbligand=CLR:'>CLR</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZHY OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Hurley, J | [[Category: Hurley, J H.]] | ||
[[Category: Im, Y | [[Category: Im, Y J.]] | ||
[[Category: Prinz, W | [[Category: Prinz, W A.]] | ||
[[Category: Raychaudhuri, S.]] | [[Category: Raychaudhuri, S.]] | ||
[[Category: CLR]] | [[Category: CLR]] | ||
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[[Category: sterol binding protein]] | [[Category: sterol binding protein]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:15:42 2008'' | ||
Revision as of 17:15, 21 February 2008
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Structure of yeast oxysterol binding protein Osh4 in complex with cholesterol
OverviewOverview
The oxysterol-binding-protein (OSBP)-related proteins (ORPs) are conserved from yeast to humans, and are implicated in the regulation of sterol homeostasis and in signal transduction pathways. Here we report the structure of the full-length yeast ORP Osh4 (also known as Kes1) at 1.5-1.9 A 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 A 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.
About this StructureAbout this Structure
1ZHY is a Single protein structure of sequence from Saccharomyces cerevisiae with and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Structural mechanism for sterol sensing and transport by OSBP-related proteins., Im YJ, Raychaudhuri S, Prinz WA, Hurley JH, Nature. 2005 Sep 1;437(7055):154-8. PMID:16136145
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