5ZM5

Crystal structure of human ORP1-ORD in complex with cholesterol at 2.6 A resolution

Summary for 5ZM5

• Entry DOI: 10.2210/pdb5zm5/pdb
• Descriptor: Oxysterol-binding protein-related protein 1, CHOLESTEROL (3 entities in total)
• Functional Keywords: transporter, complex, lipid transport
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 50367.67

Authors

Dong, J.,Wang, J.,Wu, J.W. (deposition date: 2018-04-01, release date: 2019-02-27, Last modification date: 2024-10-16)

Primary citation

Dong, J.,Du, X.,Wang, H.,Wang, J.,Lu, C.,Chen, X.,Zhu, Z.,Luo, Z.,Yu, L.,Brown, A.J.,Yang, H.,Wu, J.W.
Allosteric enhancement of ORP1-mediated cholesterol transport by PI(4,5)P2/PI(3,4)P2.
Nat Commun, 10:829-829, 2019

PubMed Abstract: Phosphatidylinositol phosphates (PIPs) and cholesterol are known to regulate the function of late endosomes and lysosomes (LELs), and ORP1L specifically localizes to LELs. Here, we show in vitro that ORP1 is a PI(4,5)P- or PI(3,4)P-dependent cholesterol transporter, but cannot transport any PIPs. In cells, both ORP1L and PI(3,4)P are required for the efficient removal of cholesterol from LELs. Structures of the lipid-binding domain of ORP1 (ORP1-ORD) in complex with cholesterol or PI(4,5)P display open conformations essential for ORP function. PI(4,5)P/PI(3,4)P can facilitate ORP1-mediated cholesterol transport by promoting membrane targeting and cholesterol extraction. Thus, our work unveils a distinct mechanism by which PIPs may allosterically enhance OSBP/ORPs-mediated transport of major lipid species such as cholesterol.

PubMed: 30783101
DOI: 10.1038/s41467-019-08791-0

Experimental method

X-RAY DIFFRACTION (2.6 Å)