Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 520, Issue 2, Pages 466-472Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2019.10.054
Keywords
Protein structure; STARD4; Sterol transport; Lipid transfer protein; Liposome; Cholesterol
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Funding
- National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2017R1A2B4004914]
- National Research Foundation of Korea [2017R1A2B4004914] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 Omega 1-loop mutant in apo forms at 1.95 and 1.7 angstrom resolutions, respectively. The structure of human STARD4 displays a conserved alpha-helix/beta-grip fold containing a deep hydrophobic pocket. The Omega 1-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 Omega 1-loop is essential for sterol binding. The human STARD4 displayed sterol transfer activity between liposomes, and the mutations in the Omega 1-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 Omega 1-loop and helix alpha 4 required for sterol transport. (C) 2019 Elsevier Inc. All rights reserved.
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