Investigators at St. Jude Children's Research Hospital turned up the heat on "disorderly" proteins and confirmed that most of these unruly molecules perform critical functions in the cell. The St. Jude team completed the first large-scale collection, investigation and classification of these so-called intrinsically unstructured proteins (IUPs), a large group of molecules that play vital roles in the daily activities of cells.
The new technique for collecting and identifying IUPs is important because although scientists have been aware of the existence of flexible proteins for many years, they have only recently realized that these molecules play major biological roles in the cell, according to Richard Kriwacki, Ph.D., an associate member of the St. Jude Department of Structural Biology. Moreover, he said, previous work by other researchers suggested that a large proportion of IUPs in mammalian cells play key roles in transmitting signals and coordinating biochemical and genetic activities that keep the cell alive and functioning. Kriwacki is senior author of a report on this work that appears in the prepublication online issue of Journal of Proteome Research.
"Until now there was no way to separate IUPs in large numbers from the more structured proteins and confirm their roles in the cell," Kriwacki said. "Our new technique selectively concentrates the IUPs that are involved in regulating functions in the cell and transmitting signals within them."
Unlike the classic description of proteins described in science textbooks, IUPs are not completely locked into rigid, 3-D shapes that determine their function in the cell. Instead, IUPs have varying amounts of flexibility within their sometimes spaghetti-like structures that is critical for function. For example, one protein named p27 initially looks like a SlinkyTM toy. However, when p27 goes to work, it puts a vise-like grip on an enzyme that otherwise would promote uncontrolled cell division.
The St. Jude team developed a technique that uses heat to isolate IUPs in large, purified quantities from extracts of a standard type of cultured mouse cells called NIH3T3 fibroblasts. The IUPs were resistant to the heat, unlike more structured proteins, which fell apart. Based on these studies, the investigators were able to classify all proteins into one of three categories: IUPs; intrinsically folded proteins (IFPs, i.e., fully folded into specific shapes); or mixed ordered or disordered proteins (MPs), which have both structured and unstructured parts.
"This work further illustrates that the disorderliness of IUPs isn't just a curiosity," said Charles Galea, Ph.D., a postdoctoral fellow in Kriwacki's lab. "This characteristic is a fundamental part of how these proteins work. So determining their exact nature, including the parts that are disordered, is an important part of understanding how they work. This is especially important in the case of IUPs linked to cancer and other diseases." The paper's first author, Galea, did much of the work on this project.
Bonnie Kourvelas | EurekAlert!
Diagnoses: When Are Several Opinions Better Than One?
19.07.2016 | Max-Planck-Institut für Bildungsforschung
High in calories and low in nutrients when adolescents share pictures of food online
07.04.2016 | University of Gothenburg
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences