Structural Studies on Cholesterol Transport

Prof. Johann Deisenhofer (University of Texas Southwestern Medical Center)

Cholesterol is essential for mammals; it is produced internally or taken up with the diet and transported in the blood stream in the form of lipoproteins, with low density lipoprotein (LDL) being most abundant. LDL is bound at cell surfaces by receptors and internalized. Inside cells, LDL particles are released from the receptors, degraded in lysosomes, and cholesterol is transported by specific binding proteins to its destinations. Prof. Deisenhofer will describe four studies on structural aspects of cholesterol transport:Electron microscopy of low density lipoprotein (LDL) with and without bound LDL receptor protein shows size, shape and internal structure of typical LDL particles. The crystal structure of the extracellular portion of human LDL receptor at pH 5.3 illustrates the domain organization of the receptor, and suggests possible mechanisms for LDL release at low pH. The recently discovered protein PCSK9 binds to the LDL receptor and appears to regulate the degradation of the receptors. A crystal structure of the complex of PCSK9 with a fragment of the LDL receptor defines the binding interface and could lead to the development of new cholesterol-lowering drugs. Mutations in the proteins NPC1 and NPC2 can cause Niemann-Pick disease by slowing down or preventing the transport of cholesterol out of lysosomes. The crystal structure of the N-terminal domain of NPC1 with and without bound cholesterol sheds light on the intra-lysosomal cholesterol transport pathway.

When 1:00pm-2:00pm, Wednesday, 18 September 2010
Where Lecture Theatre 104, New Law School

About the Speakers

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