Dynamics of crucial protein 'switch' revealedMay 18, 2011
Cell signaling networks tied to diabetes and cancer
Researchers at the University of Texas Medical Branch at Galveston and the University of California-San Diego School of Medicine have published a study that offers a new understanding of a protein critical to physiological processes involved in major diseases such as diabetes and cancer. This work could help scientists design drugs to battle these disorders.
The article was deemed a "Paper of the Week" by and will be on the cover of the Journal of Biological Chemistry. It is scheduled for publication May 20 and now available online.
"This study applied a powerful protein structural analysis approach to investigate how a chemical signal called cAMP turns on one of its protein switches, Epac2," said principal investigator Xiaodong Cheng, professor in the Department of Pharmacology and Toxicology and member of the Sealy Center for Structural Biology and Molecular Biophysics at UTMB.
The cAMP molecule controls many physiological processes, ranging from learning and memory in the brain and contractility and relaxation in the heart to insulin secretion in the pancreas. cAMP exerts its action in cells by binding to and switching on specific receptor proteins, which, when activated by cAMP, turn on additional signaling pathways.
Errors in cell signaling are responsible for diseases such as diabetes, cancer and heart failure. Understanding cAMP-mediated cell signaling, in which Epac2 is a major player, likely will facilitate the development of new therapeutic strategies specifically targeting the cAMP-Epac2 signaling components, according to the researchers.
The project involved an ongoing collaboration between Cheng's research group at UTMB, experts in the study of cAMP signaling, and UCSD professor of medicine Virgil Woods Jr. and colleagues at UCSD, pioneers in the development and application of hydrogen/deuterium exchange mass spectrometry (DXMS) technology. Compared with other protein-analysis techniques, DXMS is especially good at studying the structural motion of proteins.
Using this novel approach, the investigators were able to reveal, in fine detail, that cAMP interacts with its two known binding sites on Epac2 in a sequential fashion and that binding of cAMP changes the shape of the protein in a very specific way - switching on its activity by exposing further signaling interaction sites on Epac2.
"DXMS analysis has proved to be an amazingly powerful approach, alone or in combination with other techniques, in figuring out how proteins work as molecular machines, changing their shapes - or morphing - in the normal course of their function," said Woods. "This will be of great use in the identification and development of therapeutic drugs that target these protein motions."
Collaborators include Tamara Tsalkova and Fang Mei of the UTMB Department of Pharmacology and Toxicology; Mark A. White, associate professor in the UTMB Department of Biochemistry and Molecular Biology; and Dr. Sheng Li, Dr. Tong Liu and Daphne Wang of the UCSD Department of Medicine and Biomedical Sciences Graduate Program.
The study was funded by the National Institutes of Health and the John Sealy Memorial Endowment Fund for Biomedical Research. Based on its success at applying DXMS to the analysis of a number of important proteins, exemplified by this study with UTMB researchers, UCSD recently was awarded a generous NIH grant to implement "next-generation" advanced DXMS analysis for the benefit of scientists throughout the United States.
University of Texas Medical Branch at Galveston
Related Chemical Signal Current Events and Chemical Signal News Articles
Molecular switch for cheaper biofuel
Lignocellulosic waste such as sawdust or straw can be used to produce biofuel - but only if the long cellulose and xylan chains can be successfully broken down into smaller sugar molecules.
Clues to heart disease in unexpected places, Temple researchers discover
A major factor in the advance of heart disease is the death of heart tissue, a process that a team of scientists at Temple University School of Medicine's (TUSM) Center for Translational Medicine think could be prevented with new medicines.
Surf's up: Turbulence tells sea urchins to settle down
Tumbling in the waves as they hit a rocky shore tells purple sea urchin larvae it's time to settle down and look for a spot to grow into an adult, researchers at the University of California, Davis, Bodega Marine Laboratory have found.
New findings into conquering influenza
Reseachers from the University of Melbourne and The Walter and Eliza Hall Institute (WEHI) have discovered a new protein that protects against viral infections such as influenza.
Crayfish species proves to be the ultimate survivor
One of the most invasive species on the planet is able to source food from the land as well as its usual food sources in the water, research from Queen Mary, University of London has found.
Plant perfumes woo beneficial bugs
Scientists funded by the Biotechnology and Biological Sciences Research Council (BBSRC) have discovered that maize crops emit chemical signals which attract growth-promoting microbes to live amongst their roots.
Orientation of desert ants: Every cue counts
Desert ants have adapted to a life in a barren environment which only provides very few landmarks for orientation.
From 'Refrigerator Mothers' to untangling the genetic roots of autism
With the "Refrigerator Mother" notion about the cause of autism a distant and discredited memory, scientists are making remarkable progress in untangling the genetic roots of the condition, which affects millions of children and adults, according to an article in the current edition of Chemical & Engineering News.
Carp dominate crayfish in invasive species battleground
Louisiana red swamp crayfish and common carp are two of the most invasive species on the planet yet how they interact has only recently been revealed by scientists at Queen Mary, University of London.
Manipulating way bacteria 'talk' could have practical applications, Texas A&M profs say
By manipulating the way bacteria "talk" to each other, researchers at Texas A&M University have achieved an unprecedented degree of control over the formation and dispersal of biofilms - a finding with potentially significant health and industrial applications, particularly to bioreactor technology.
More Chemical Signal Current Events and Chemical Signal News Articles