Jianhan Chen, an assistant professor of biochemistry, was one of the researchers on a collaborative project that took a combined computational and experimental approach to understand how protein p21 functions as a versatile regulator of cell division. Their latest findings, "Intrinsic disorder mediates the diverse regulatory functions of the Cdk inhibitor p21," were published in a recent edition of Nature Chemical Biology.
The study used computer simulation to rationalize results from biochemical and biophysical experiments, and provided further insights that would guide future investigations, Chen said. In this case, the focus is human protein p21 and its ability to function as an inhibitor of normal cell growth.
The protein has been shown to be an intrinsically disordered protein. This means it lacks a well-defined three-dimensional structure, characteristics that, until roughly a decade ago, were thought to be necessary for the protein to function.
"For a long time it was believed that proteins must fold to function and it was hard to imagine how an unfolded protein could play a role in crucial cellular areas," Chen said. "What researchers before me found was that by lacking a stable structure, this actually turned out to be really, really important to how these proteins function."
Along with being an intrinsically disordered protein, p21 is a versatile cyclin-dependent kinase, or Cdk, inhibitor -- meaning it adapts to and inhibits a range of Cdk-cyclin complexes that regulate eukaryote cell division. It also has been connected to cancer and aging. For example, Chen said p21 is a principal trans-activation target of the p53 tumor suppressor protein and contributes to p53-dependent tumor suppression.
"This protein is extremely challenging to study. It's highly dynamic and it's heterogeneous," Chen said. Because of this, mechanistic studies of intrinsically disordered proteins like p21 have been limited. Experiment alone is not sufficient and computer modeling is necessary to provide important missing details, he said. A tight integration of both could lead to a precise understanding of how structural flexibility influences function of p21 and other intrinsically disordered proteins.
"For me this is one of the most interesting IDPs," Chen said. "I'm a theorist and I want to use this system to understand the principles of how this type of proteins can perform their functions. Even though they are disordered, they are not random; there is no chaos. They still have some type of residual structures and certain features which allow function to be controlled in a precise way, and I want to understand the underlying mechanism of how this occurs."
Chen is continuing work with p21 and other small proteins that regulate cell cycles.
In 2010 Chen received more than $670,000 as a CAREER Award from the National Science Foundation. CAREER is the foundation's most prestigious award for junior faculty to support early development activities of teach-scholars who most effectively integrate research and education within the context of the organization's mission. He and his lab focus on computer modeling to understand how biomolecules perform their biological functions.
Jianhan Chen | EurekAlert!
Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University
Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
25.04.2017 | Physics and Astronomy
25.04.2017 | Materials Sciences
25.04.2017 | Life Sciences