Biological complexity: how cholesterol enters cells (Introduction)

by David Turell , Monday, September 23, 2019, 01:42 (1668 days ago) @ David Turell

Cholesterol is carried in the blood and must enter cells to be used. A very complex protein mechanism is shown:

https://www.sciencedaily.com/releases/2019/09/190920111345.htm

"Most people have heard of "cholesterol levels" and the dangers of high blood cholesterol, which is one of the main causes of cardiovascular disease. But besides the harmful side effects of high cholesterol, cholesterol is an essential component of all cells and fundamental to a host of important functions of the body. Hormones like estrogen and testosterone are made from cholesterol, for example.

"It has been known for a long time that cholesterol is transported around the body in the blood as small particles consisting of fat and protein. In the body's cells, these particles are broken down and cholesterol is released and integrated as part of the cell. Although this process is essential, not just for humans, but for all animals and plants, surprisingly little is known about how cholesterol is actually incorporated into the cells after the breakdown of these particles.

From the study itself:

https://www.cell.com/cell/fulltext/S0092-8674(19)30957-2?_returnURL=https%3A%2F%2Flinki...

Summary: "Niemann-Pick type C (NPC) proteins are essential for sterol homeostasis, believed to drive sterol integration into the lysosomal membrane before redistribution to other cellular membranes. Here, using a combination of crystallography, cryo-electron microscopy, and biochemical and in vivo studies on the Saccharomyces cerevisiae NPC system (NCR1 and NPC2), we present a framework for sterol membrane integration. Sterols are transferred between hydrophobic pockets of vacuolar NPC2 and membrane-protein NCR1. NCR1 has its N-terminal domain (NTD) positioned to deliver a sterol to a tunnel connecting NTD to the luminal membrane leaflet 50 Å away. A sterol is caught inside this tunnel during transport, and a proton-relay network of charged residues in the transmembrane region is linked to this tunnel supporting a proton-driven transport mechanism. We propose a model for sterol integration that clarifies the role of NPC proteins in this essential eukaryotic pathway and that rationalizes mutations in patients with Niemann-Pick disease type C."

Comment: The description is difficult to follow. Look at the diagram on the website to see how complex is this protein arrangement. Not by chance. Requires design in the very beginning of this geologic period for organisms like the Cambrian animals to have survived.