The study, led by W. Sean Davidson, PhD, professor in UC's pathology and laboratory medicine department, appears online ahead of print March 13, 2011, in the journal Nature Structural & Molecular Biology.
HDL (high-density lipoproteins) also known as "good cholesterol," are packets of protein and fat that deliver fat to specific locations within the body.
There is an increasing effort to create drugs that help to raise levels of HDL working in conjunction with existing drugs that lower "bad cholesterol," or low-density lipoproteins (LDL).
Studies of synthetically derived HDL have shown that an abundant protein in HDL, apolipoprotein A-I, plays a key role in HDL's cardioprotective anti-inflammatory and anti-oxidative properties.
"Unfortunately, we've known very little about the molecular details that explain HDL's protective effects," says Davidson. "A major reason for this is an almost complete lack of understanding of HDL's structure and how it interacts with other important plasma factors."
Rong Huang, PhD, a post-doctoral fellow in Davidson's laboratory, has isolated human HDL and analyzed its 3-D structure as it circulates in human plasma.
"Previous studies have only focused on synthetic HDL made in the test tube," Davidson says. "By isolating human HDL, we were able to focus on the broad range of HDL particles actually circulating in humans."
Team members used a series of sophisticated spectroscopic and mass spectrometric techniques to study HDL and have found that proteins of HDL form a cage-like structure that encapsulates its fatty cargo.
They determined that most of the HDL particles circulating in human plasma are remarkably similar in structure; however, they found evidence that the particles have a twisting or shock absorber-like motion that allows them to adapt to changes in particle fat content.
By determining the structure of HDL, Davidson and his team were able to conclude that the majority of physiological interactions occurring with HDL—including its twisting movements—occur at the particle surface, which is dominated by the cardioprotective protein apolipoprotein A-I.
This monopolization of the particle surface, Davidson says, suggests that other proteins have very little room to bind to HDL and probably have to interact with the protein itself, which could explain how apolipoprotein A-I plays such a dominant role in HDL function and its protective effects.
"This work presents the first detailed models of human plasma HDL and has important implications for understanding key interactions in plasma that modulate its protective functions in the context of cardiovascular disease," says Davidson.
The study was funded by grants from the National Institutes of Health and its National Heart, Lung, and Blood Institute, as well as funds from the American Heart Association.
Dama Ewbank | EurekAlert!
Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University
DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.
Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
15.12.2017 | Power and Electrical Engineering
15.12.2017 | Materials Sciences
15.12.2017 | Life Sciences