Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists solve structure of key protein in innate immune response

22.03.2005


When bacteria invade the body, a molecule called CD14 binds to substances liberated from the bacteria and initiates the cellular defense mechanisms. In a report published in the Journal of Biological Chemistry, scientists in Korea announced their elucidation of three-dimensional structure of CD14 and showed how it is perfectly suited to bind to certain bacterial products.



The research appears as the "Paper of the Week" in the March 25 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

The innate immune system uses the CD14 receptor protein to recognize several microbial and cellular products including lipopolysaccharide (LPS), a glycolipid found on the outer membrane of certain bacteria. Once CD14 binds to LPS or another ligand, it presents the molecule to other proteins which initiate a strong pro-inflammatory response that stimulates host defenses.


"Macrophages and monocytes can recognize distinct structural patterns in various molecules from pathogenic microorganisms," explains Dr. Jie-Oh Lee of the Korea Advanced Institute of Science and Technology. "LPS is the most famous and probably the most important inducer of the innate immune response."

Dr. Lee and his colleagues solved the three-dimensional crystal structure of CD14, providing crucial insights into how the receptor binds to its ligands. "Our structure shows that CD14 has a large hydrophobic pocket near its amino terminus," says Dr. Lee. "We propose that this pocket is the main binding site for LPS because previous biochemical studies demonstrate that amino acid residues comprising the pocket are critical for LPS binding. Most, if not all, of the CD14 ligands compete with LPS for CD14 binding. Therefore, they probably share the same binding pocket with LPS."

Ligands other than LPS can be accommodated in the pocket due to its large size, the flexibility of its rim, and the multiple grooves available for ligand binding. The researchers also discovered that mutations that interfere with LPS signaling cluster in a separate area near the pocket suggesting that the areas around the pocket are important in LPS transfer.

Not only do these findings shed light on how cells recognize pathogens, they also may also lead to the development of drugs to help treat septic shock, an often fatal systemic bacterial infection that is triggered by LPS.

"Pharmaceutical companies have tried to develop anti-septic shock agents for a long time without clear success," explains Dr. Lee. "Since LPS is an important inducer of septic shock, blocking LPS receptors such as CD14 are among the most important targets. Our structure shows the shape of the LPS binding pocket of CD14. Now, drug developers will have better chance to design a molecule that will complement the shape of the pocket."

Nicole Kresge | EurekAlert!
Further information:
http://www.jbc.org
http://www.asbmb.org

More articles from Life Sciences:

nachricht Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>