6L1M

Structure of human StAR-related lipid transfer protein 4 mutant - LWNI107-110GG

Summary for 6L1M

• Entry DOI: 10.2210/pdb6l1m/pdb
• Descriptor: StAR-related lipid transfer protein 4 (2 entities in total)
• Functional Keywords: stard4, lipid transport, sterol, cholesterol, lipid transfer protein, transport protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 23472.48

Authors

Tong, J.,Im, Y.J. (deposition date: 2019-09-29, release date: 2019-10-30, Last modification date: 2023-11-22)

Primary citation

Tan, L.,Tong, J.,Chun, C.,Im, Y.J.
Structural analysis of human sterol transfer protein STARD4.
Biochem.Biophys.Res.Commun., 520:466-472, 2019

PubMed Abstract: The steroidogenic acute regulatory protein (StAR)-related lipid transfer domain-4 (STARD4) is a sterol-binding protein that is involved in cholesterol homeostasis by intracellular sterol transport. In this work, we determined the crystal structures of human STARD4 and its Ω1-loop mutant in apo forms at 1.95 and 1.7 Å resolutions, respectively. The structure of human STARD4 displays a conserved α-helix/β-grip fold containing a deep hydrophobic pocket. The Ω1-loop which serves as a lid for the hydrophobic pocket has a closed conformation. The shape of the sterol-binding cavity in the closed form is not complementary to accommodate cholesterol, suggesting that a conformational change of the Ω1-loop is essential for sterol binding. The human STARD4 displayed sterol transfer activity between liposomes, and the mutations in the Ω1-loop and the hydrophobic wall abolished the transfer activity. This study confirms the structural conservation of the STARD4 subfamily proteins and the flexibility of the Ω1-loop and helix α4 required for sterol transport.

PubMed: 31607485
DOI: 10.1016/j.bbrc.2019.10.054

Experimental method

X-RAY DIFFRACTION (1.7 Å)