Structure of Yeast OSBP-Related Protein Osh1 Reveals Key Determinants for Lipid Transport and Protein Targeting at the Nucleus-Vacuole Junction.
Yeast Osh1 belongs to the oxysterol-binding protein (OSBP) family of proteins and contains multiple targeting modules optimized for lipid transport at the nucleus-vacuole junction (NVJ). The key determinants for NVJ targeting and the role of Osh1 at NVJs have remained elusive because of unknown lipid specificities. In this study, we determined the structures of the ankyrin repeat domain (ANK), and OSBP-related domain (ORD) of Osh1, in complex with Nvj1 and ergosterol, respectively. The Osh1 ANK forms a unique bi-lobed structure that recognizes a cytosolic helical segment of Nvj1. We discovered that Osh1 ORD binds ergosterol and phosphatidylinositol 4-phosphate PI(4)P in a competitive manner, suggesting counter-transport function of the two lipids. Ergosterol is bound to the hydrophobic pocket in a head-down orientation, and the structure of the PI(4)P-binding site in Osh1 is well conserved. Our results suggest that Osh1 performs non-vesicular transport of ergosterol and PI(4)P at the NVJ.
College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea.
Mohammad Kawsar
MK
Manik
College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea.
Huiseon
H
Yang
College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea.
Junsen
J
Tong
College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea. Electronic address: imyoungjun@jnu.ac.kr.
Young Jun
YJ
Im
D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D004875:Ergosterol / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D014617:Vacuoles / Q000378:metabolism; D015003:Yeasts / Q000378:metabolism*
D005656:Fungal Proteins; D018129:Phosphatidylinositol Phosphates; C037178:phosphatidylinositol 4-phosphate; D004875:Ergosterol
ankyrin repeat; crystal structure; ergosterol; lipid transport; nucleus-vacuole junction; oxysterol-binding protein; phosphoinositide