Wednesday, December 18, 2013

Advanced Spectroscopy Technique Allows Scientists to Analyze Protein Structure with Infrared Light

Proteins come in many forms and are essential for cellular function. Each protein has a defined structure that is necessary for the protein to perform its function. The most common structures found in proteins are alpha helices and beta pleated sheets. Disruption of the normal common structures in a protein is associated with diseases such as Alzheimer or Parkinsons disease.

Interferometer for FTIR
Until now spectroscopic techniques lacked the sensitivity to analyze protein structure. However, a recent paper published in Nature Communications describes the work of European scientist using a technique called Fourier transform infrared nanospectroscopy (nano FTIR) that allows mapping of protein structure with a 30 nm resolution. This allowed them to identify the structure of proteins in a complex or to identify the protein structures characteristic of a virus (alpha helices) mixed in with insulin fibrils (beta pleated sheets).

The authors believe that this approach will be very useful, with the potential to map the structure of cellular receptors and proteins within complexes.

Original article: Structural analysis and mapping of individual protein complexes by infrared nanospectroscopy

Some information for this blog was obtained from: Infrared Sheds Light On Single Protein Complexes

Tuesday, December 17, 2013

Newly Discovered Regulation of KRas may Result in Novel Cancer Therapies

KRas has been well characterized for its role in several cancers. Mutations of KRas are seen in more than 90% of pancreatic cancer patients, and are prevalent in colon and lung cancer. However, targeting KRas for cancer therapy has been difficult.

Now, an international collaboration of scientists has revealed a new mechanism for regulating KRas function that they hope will provide a new approach for identification of therapeutic targets in cancers with a KRas mutation. Their findings are published in a recent issue of JBC in the article entitled: 'Degradation of Activated K-Ras Orthologue via K-Ras Specific Lysine Residues is Required for Cytokinesis'

This article describes the use of a social ameboid, Dictyostelium, as a powerful model system to study Ras signaling and KRas regulation. They introduced the cancer causing (oncogenic) form of KRas into Dictyostelium, and compared its regulation with normal KRas. They found that these cells recognize the oncogenic KRas and mark it by ubiquitination. Ubiquitination is a process that cells normally use to mark a protein that needs to be recycled, so the ubiquitination of oncogenic KRas leads to it being chopped up and cleared from cells.

The next step is to identify the protein that ubiquitinates oncogenic KRas so that its activity can be increased in cancer cells with mutated KRas.

Some information for this blog was obtained from: Regulation of Cancer-Causing Protein Could Lead to New Therapeutic Targets

Monday, December 16, 2013

Scientists study essential enzyme to better understand molecular evolution

Scientists at the University of Iowa analyzed various forms of the enzyme dihydrofolate reductase (DHFR) using bioinformatics, computer-based calculations, artificial mutagenesis and kinetic measurements. The result of their work is published in the recent JBC paper entitled: 'Preservation of Protein Dynamics in Dihydrofolate Reductase Evolution'.

DHFR with dihydrofolate (left)
and NADPH (right) bound

The scientists chose DHFR due to its well characterized role and the fact that it is present in nearly all organisms. DHFR is involved in DNA biosynthesis and cell replication, therefore, it is essential to survival. Indeed, DHFR has been targeted in several therapeutic applications where antagonists have been used as anti-cancer treatments and anti-bacterial agents.

The results of the current paper showed that although bacteria and human DHFR are different in terms of genetic and protein sequence, the chemical conversion performed by this enzyme is quite well conserved. Indeed the bacterial enzyme already has reactants perfectly aligned in its active site! This was quite surprising as the human enzyme is not only genetically different but much faster.

The results of this work are important in the design of drugs against DHFR and the design of catalysts that are inspired by nature.

Some information for this blog was obtained from: 'Evolution On Molecular Level'