Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers uncover key interaction in cholesterol regulation

05.02.2008
Researchers at UT Southwestern Medical Center have determined the specific way in which a destructive protein binds to and interferes with a molecule that removes low-density lipoproteins (LDL), the so-called “bad” cholesterol, from the blood.

“The practical benefit of this finding is that we can now search for new ways to lower cholesterol by designing targeted antibodies to disrupt this interaction,” said Dr. Jay Horton, professor of internal medicine and molecular genetics and a senior author of the study, which appears online this week in the Proceedings of the National Academy of Sciences.

The protein, called PCSK9, has emerged as an important regulator of “bad” cholesterol in the blood, said Dr. Horton, whose research focuses in part on understanding the protein’s function.

PCSK9 disrupts the activity of a key molecule called the low-density lipoprotein receptor, or LDLR. This molecule, which juts out from the surface of cells, latches on to “bad” cholesterol in the bloodstream and removes it by drawing it into the cells.

... more about:
»Interaction »LDL »LDLR »PCSK9 »receptor

The PCSK9 protein also can latch on to the LDL receptor. This binding, however, triggers a chain of biochemical reactions that leads to the destruction of the LDL receptor. With fewer receptors available, more “bad” cholesterol remains in the bloodstream.

“You want to have LDL receptors to clear LDL from the blood – that’s a good thing,” Dr. Horton said. “So you don’t want to have PCSK9; it normally functions in a harmful way.”

Too much LDL cholesterol in the blood is a major risk factor for heart disease, heart attack and stroke because it contributes to the buildup of plaque that clogs the walls of arteries. More than 25 million people worldwide take a class of drugs called statins to lower their cholesterol to within recommended healthy levels.

To determine exactly how PCSK9 and the LDLR physically interact, the researchers, led by Dr. Hyock Joo Kwon, an instructor in biochemistry, collaborated with Dr. Johann Deisenhofer, professor of biochemistry, an investigator with the Howard Hughes Medical Institute and a senior author of the study. Dr. Deisenhofer shared the 1988 Nobel Prize in Chemistry for his work in discovering the structure of a key protein involved in photosynthesis.

Using X-rays bounced off crystals made up of both PCSK9 and a portion of the LDLR protein, the researchers identified small regions of each protein that attach to each other. They then created a detailed structural model of the area.

“It looks like those portions are absolutely essential for the interaction to take place,” Dr. Horton said.

The researchers are now designing antibodies and small chains of peptides – the building blocks of proteins – that have the ability to jam the interaction between LDLR and PCSK9.

Dr. Horton’s previous studies have shown that mice lacking PCSK9 have LDL cholesterol levels less than half that of normal mice.

Studies by other UT Southwestern researchers have found that people with mutations in the PCSK9 gene, which prevented them from making normal levels of the PCSK9 protein, had LDL cholesterol levels 28 percent lower than individuals without the mutation and were protected from developing coronary heart disease. That research was led by Dr. Jonathan Cohen, professor of internal medicine, and Dr. Helen Hobbs, director of the Eugene McDermott Center for Human Growth and Development.

While statin drugs work by increasing the number of LDL receptors on cells, a drug targeting PCSK9 might prevent the existing receptors from being degraded.

“These studies suggest that inhibiting PCSK9’s action may be another route to lowering LDL cholesterol in individuals with high cholesterol,” said Dr. Horton.

Aline McKenzie | EurekAlert!
Further information:
http://www.utsouthwestern.edu
http://www.utsouthwestern.org/patientcare/medicalservices/hlv.html

Further reports about: Interaction LDL LDLR PCSK9 receptor

More articles from Life Sciences:

nachricht Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>