Cholesterol, a waxy substance incriminated in heart attack and stroke, is a precious commodity for cells. In fact, errors in a cell’s ability to import these rod-like molecules can be fatal. In new work, researchers at The Rockefeller University and their colleagues delved into a pivotal phase in the process by which cells prepare to use cholesterol they have taken in. The scientists’ detailed study of two molecules that help ferry cholesterol within cells appeared recently in PNAS. The first article was published on July 19, 2016 and titled “Structure of Human Niemann–Pick C1 Protein.” The second article was published on September 6, 2016 and titled “Clues to the Mechanism of Cholesterol Transfer from the Structure of NPC1 Middle Lumenal Domain Bound to NPC2.” “Because cholesterol is essential, but potentially dangerous, the body and its cells have carefully orchestrated systems for making sure the right amount of cholesterol goes only to the right places,” says corresponding author Günter Blobel, Head of the Laboratory of Cell Biology. Dr. Blobel was the sole recipient of the 1999 Nobel Prize in Physiology or Medicine for his discovery that proteins have intrinsic signals that govern their transport and localization in the cell. Dr. Blobel is the John D. Rockefeller Jr. Professor at the Rockefeller and a Howard Hughes Medical Institute investigator. “By examining the structures and interaction of two cholesterol-transporting proteins in unprecedented detail, we now better understand an aspect of this complex process: i.e., how cells prepare to properly use cholesterol they have imported,” Dr. Blobel says. The research might also help explain the details of how the Ebola virus, the cause of an often-fatal disease that comes with fever and bleeding, penetrates a host cell.
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