A vertebrate model for the study of lipid binding/transfer protein function: Conservation of OSBP-related proteins between zebrafish and human
- Authors
- Zhou, Y., Wohlfahrt, G., Paavola, J., and Olkkonen, V.M.
- ID
- ZDB-PUB-140210-11
- Date
- 2014
- Source
- Biochemical and Biophysical Research Communications 446(3): 675-80 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Carrier Proteins/metabolism*
- Conserved Sequence
- Glycerophospholipids/metabolism
- Humans
- Lipid Metabolism*
- Phosphatidylinositol Phosphates/metabolism
- Protein Conformation
- Protein Structure, Tertiary
- Receptors, Steroid/metabolism*
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/metabolism*
- PubMed
- 24326072 Full text @ Biochem. Biophys. Res. Commun.
Oxysterol-binding protein (OSBP) and OSBP-related (ORP) or OSBP-like (OSBPL) proteins constitute a family of lipid-binding/transfer proteins (LTPs) present in eukaryotes from yeast to man. The mechanisms of ORP function have remained incompletely understood. However, several ORPs are present at membrane contact sites and act as either lipid transporters or sensors that control lipid metabolism, cell signaling, and vesicle transport. Zebrafish, Danio rerio, has gained increasing popularity as a model organism in developmental biology, human disease, toxicology, and drug discovery. However, LTPs in the fish are thus far unexplored. In this article we report a series of bioinformatic analyses showing that the OSBPL gene family is highly conserved between the fish and human. The OSBPL subfamily structure is markedly similar between the two organisms, and all 12 human genes have orthologs, designated osbpl and located on 11 chromosomes in D. rerio. Interestingly, osbpl2 and osbpl3 are present as two closely related homologs (a and b), due to gene duplication events in the teleost lineage. Moreover, the domain structures of the distinct ORP proteins are almost identical between zebrafish and man, and molecular modeling in the present study suggests that ORD liganding by phosphatidylinositol-4-phosphate (PI4P) is a feature conserved between yeast Osh3p, human ORP3, and zebrafish Osbpl3. The present analysis identifies D. rerio as an attractive model to study the functions of ORPs in vertebrate development and metabolism.