Oxysterol-Binding Protein 1

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OSBP
OSBP
according to PDB  4IC4

Existing structural data : 4IC4

Properties of human protein
Mass / length primary structure 807 amino acids , 89,421 daltons
Secondary to quaternary structure Homodimer , homotrimer
Identifier
Gene name OSBP
External IDs

The Oxysterol-binding protein 1 (OSBP) is a transport protein for lipids , especially for oxidized steroids .

properties

OSBP1 is involved in the transport of lipids between the Golgi apparatus and the endoplasmic reticulum in the cytosol of eukaryotic cells and forms a lipid transporter between these cell organelles . An oxysterol is given to the Golgi apparatus in exchange for phosphatidylinositol-4-phosphate (PI4P). The PI4P is then dephosphorylated in the endoplasmic reticulum by the phosphatase SAC1 / SACM1L.

OSBP binds cholesterol and a number of oxysterols including 25-hydroxycholesterol . After binding of cholesterol, PP2A and a tyrosine phosphatase are bound to a protein complex that dephosphorylates ERK1 and ERK2 . 25-hydroxycholesterol dissolves the complex again. OSBP1 reduces the stability of ABCA1 and thereby regulates the exocytosis of cholesterol. The gene expression of SREBP1c is regulated by OSBP. OSBP1 also binds to JAK2 / STAT3 .

regulation

OSBP1 is dephosphorylated by protein kinase D. The activity of OSBP1 is also inhibited by 25-hydroxycholesterol; OSBP1 then changes from the cytosol to the membrane of the endoplasmic reticulum.

structure

OSBP1 has the protein domains Pleckstrin Homology Domain (PH) at the N terminus , an FFAT domain (two phenylalanines in a sequence of acidic amino acids and an ORD domain at the C terminus ). The PH binds PI4P and GTP- bound Arf1 . As a result, OSBP1 forms a molecular bridge between ER and Golgi. The FFAT domain binds to VAP ( vesicle-associated membrane protein associated protein ).

Isoforms

OSBP is the first described representative of the OSBP-related proteins (ORP), of which mammals have 16 isoforms . There are 7 isoforms in yeast.

Individual evidence

  1. ↑ a b c B. Mesmin, J. Bigay, J. Moser von Filseck, S. Lacas-Gervais, G. Drin, B. Antonny: A four-step cycle driven by PI (4) P hydrolysis directs sterol / PI ( 4) P exchange by the ER-Golgi tether OSBP. In: Cell . Volume 155, Number 4, November 2013, pp. 830-843, doi : 10.1016 / j.cell.2013.09.056 , PMID 24209621 .
  2. ↑ M. Weber-Boyvat, W. Zhong, D. Yan, VM Olkkonen: Oxysterol-binding proteins: functions in cell regulation beyond lipid metabolism. In: Biochemical pharmacology. Volume 86, Number 1, July 2013, pp. 89-95, doi : 10.1016 / j.bcp.2013.02.016 , PMID 23428468 .
  3. ↑ VM Olkkonen: OSBP-Related Protein Family in Lipid Transport Over Membrane Contact Sites. In: Lipid insights. Volume 8, Suppl 1 2015, pp. 1-9, doi : 10.4137 / LPI.S31726 , PMID 26715851 , PMC 4685180 (free full text).
  4. ^ A b Ping-yuan Wang, Jian Weng, Richard GW Anderson: OSBP Is a Cholesterol-Regulated Scaffolding Protein in Control of ERK1 / 2 Activation . In: Science . tape 307 , no. 5714 , March 4, 2005, p. 1472–1476 , doi : 10.1126 / science.1107710 ( PDF ). PDF ( Memento of the original from July 3, 2016 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.  @1@ 2Template: Webachiv / IABot / www.pdf-archive.com
  5. ↑ M. Suchanek, R. Hynynen, G. Wohlfahrt, M. Lehto, M. Johansson, H. Saarinen, A. Radzikowska, C. Thiele, VM Olkkonen: The mammalian oxysterol-binding protein-related proteins (ORPs) bind 25 -hydroxycholesterol in an evolutionarily conserved pocket. In: Biochemical Journal . Volume 405, number 3, August 2007, pp. 473-480, doi : 10.1042 / BJ20070176 , PMID 17428193 , PMC 2267293 (free full text).
  6. ^ K. Bowden, ND Ridgway: OSBP negatively regulates ABCA1 protein stability. In: The Journal of biological chemistry. Volume 283, Number 26, June 2008, pp. 18210-18217, doi : 10.1074 / jbc.M800918200 , PMID 18450749 .
  7. ↑ D. Yan, M. Lehto, L. Rasilainen, J. Metso, C. Ehnholm, S. Ylä-Herttuala, M. Jauhiainen, VM Olkkonen: Oxysterol binding protein induces upregulation of SREBP-1c and enhances hepatic lipogenesis. In: Arteriosclerosis, thrombosis, and vascular biology. Volume 27, Number 5, May 2007, pp. 1108-1114, doi : 10.1161 / ATVBAHA.106.138545 , PMID 17303778 .
  8. ^ GR Romeo, A. Kazlauskas: Oxysterol and diabetes activate STAT3 and control endothelial expression of profilin-1 via OSBP1. In: The Journal of biological chemistry. Volume 283, Number 15, April 2008, pp. 9595-9605, doi : 10.1074 / jbc.M710092200 , PMID 18230613 .
  9. ↑ S. NHEK, M. Ngo, X. Yang, MM Ng, SJ Field, JM Asara, ND Ridgway, A. Toker: Regulation of oxysterol-binding protein Golgi localization through protein kinase D-mediated phosphorylation. In: Molecular biology of the cell. Volume 21, number 13, July 2010, pp. 2327-2337, doi : 10.1091 / mbc.E10-02-0090 , PMID 20444975 , PMC 2893995 (free full text).
  10. ^ ND Ridgway, PA Dawson, YK Ho, MS Brown, JL Goldstein: Translocation of oxysterol binding protein to Golgi apparatus triggered by ligand binding. In: Journal of Cell Biology . Volume 116, Number 2, January 1992, pp. 307-319, PMID 1730758 , PMC 2289278 (free full text).
  11. ^ SE Kaiser, JH Brickner, AR Reilein, TD Fenn, P. Walter, AT Brunger: Structural basis of FFAT motif-mediated ER targeting. In: Structure (London, England: 1993). Volume 13, Number 7, July 2005, pp. 1035-1045, doi : 10.1016 / j.str.2005.04.010 , PMID 16004875 .
  12. ↑ VM Olkkonen, TP Levine: Oxysterol binding proteins: in more than one place at one time? In: Biochemistry and cell biology = Biochimie et biologie cellulaire. Volume 82, Number 1, February 2004, pp. 87-98, doi : 10.1139 / o03-088 , PMID 15052330 (review).