Features Partner Sites Information LinkXpress
Sign In
Demo Company

Pathogens Remove Myristic Acid from Immune Cell Signaling Proteins

By BiotechDaily International staff writers
Posted on 15 Apr 2013
Print article
Image: Shigella flexneri (Photo courtesy of Bacteria in Photos).
Image: Shigella flexneri (Photo courtesy of Bacteria in Photos).
An enzyme produced by the pathogenic bacterium Shigella flexneri selectively removes a fatty acid from certain membrane proteins and modifies their behavior in a fashion that disables the immune system’s communication infrastructure.

Myristic acid, a 14-carbon fatty acid, is commonly added to the penultimate, nitrogen-terminus, glycine residue in receptor-associated kinases to confer the membrane localization of the enzyme. The myristic acid has a sufficiently high hydrophobicity to become incorporated into the fatty acyl core of the phospholipid bilayer of the plasma membrane of the eukaryotic cell. In this way, myristic acid acts as a lipid anchor in biomembranes. This modification is conserved across eukaryotic species and occurs on nearly 1% of the cellular proteome. Addition of myristic acid to proteins (myristoylation) has received a lot of attention from researchers due to its crucial role in the transformation of normal cells to cancer cells and for promoting cancer cell growth.

Some pathogenic organisms avoid immune system responses by removing myristic acid from immune cell membrane proteins (demyristoylation) and thereby disrupting communication among the various types of immune cells. Investigators at the University of Texas Southwestern Medical Center (Dallas, USA) described in the April 4, 2013, issue of the journal Nature an irreversible mechanism of protein demyristoylation catalyzed by IpaJ (invasion plasmid antigen J), a previously uncharacterized Shigella flexneri type III effector protein with cysteine protease activity.

They reported that mass spectrometry had showed that IpaJ cleaved the peptide bond between N-myristoylated glycine-2 and asparagine-3 of human ARF1 (ADP-ribosylation factor), thereby providing a new mechanism for host secretory inhibition by a bacterial pathogen. In addition, they showed that IpaJ cleaved an array of N-myristoylated proteins involved in cellular growth, signal transduction, autophagasome maturation, and organelle function.

“Our findings provide insight into severe bacterial infectious diseases, as well as some forms of cancer, in which the attachment of fat molecules to proteins is an essential feature of the disease process,” said senior author Dr. Neal Alto, assistant professor of microbiology at the University of Texas Southwestern Medical Center.

“Normally, a macrophage will engulf an invading bacteria and send out cytokines, proteins that act as cellular alert signals, which in turn recruit more immune cells to the site of infection,” said Dr. Alto. “When the macrophages engulf Shigella, however, the bacteria use IpaJ to cut fatty acids from proteins, which need those fats attached in order to sound the alarm. Doing so buys more time for the bacteria to grow and survive. It is very interesting from a disease process point of view, but it is also important because we now have a potential drug target. The next step will be to identify small molecule inhibitors that are specific to this fat-snipping protease and that might be developed into drugs.”

Related Links:

University of Texas Southwestern Medical Center

Print article



view channel
Image: A partially completed three-dimensional printed airway from nostril to trachea with fine structure of the nasal cavity showing (Photo courtesy of Dr. Rui Ni, Pennsylvania State University).

The Structure of the Nasal Cavity Channels Food Smells into the Nose and Avoids the Lungs

Three-dimensional printing technology was used to create a model of the nasal cavity that enabled researchers to demonstrate why the smell of food goes into the nose rather than down into the lungs.... Read more


view channel

Molecular Light Shed on “Dark” Cellular Receptors

Scientists have created a new research tool to help find homes for orphan cell-surface receptors, toward better understanding of cell signaling, developing new therapeutics, and determining causes of drug side-effects. The approach may be broadly useful for discovering interactions of orphan receptors with endogenous, naturally... Read more

Lab Technologies

view channel
Image:  The BioSpa 8 Automated Incubator (Photo courtesy of BioTek Instruments).

Smart Incubator System Automates Live Cell Assay Operations

A new instrument that automates laboratory workflow by linking microplate washers and dispensers with readers and imaging systems is now available for biotech and other life sciences researchers.... Read more


view channel

Purchase of Biopharmaceutical Company Will Boost Development of Nitroxyl-Based Cardiovascular Disease Drugs

A major international biopharmaceutical company has announced the acquisition of a private biotech company that specializes in the development of drugs for treatment of cardiovascular disease. Bristol-Myers Squibb Co. (New York, NY, USA) has initiated the process to buy Cardioxyl Pharmaceuticals Inc. (Chapel Hill, NC, USA).... Read more
Copyright © 2000-2015 Globetech Media. All rights reserved.