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Publication Abstract from PubMed

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 Omega1-loop mutant in apo forms at 1.95 and 1.7A resolutions, respectively. The structure of human STARD4 displays a conserved alpha-helix/beta-grip fold containing a deep hydrophobic pocket. The Omega1-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 Omega1-loop is essential for sterol binding. The human STARD4 displayed sterol transfer activity between liposomes, and the mutations in the Omega1-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 Omega1-loop and helix alpha4 required for sterol transport.

Structural analysis of human sterol transfer protein STARD4.,Tan L, Tong J, Chun C, Im YJ Biochem Biophys Res Commun. 2019 Oct 10. pii: S0006-291X(19)31941-2. doi:, 10.1016/j.bbrc.2019.10.054. PMID:31607485^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.