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!
Zap! Graphene is bad news for bacteria
23.05.2017 | Rice University
Discovery of an alga's 'dictionary of genes' could lead to advances in biofuels, medicine
23.05.2017 | University of California - Los Angeles
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...
23.05.2017 | Event News
22.05.2017 | Event News
17.05.2017 | Event News
23.05.2017 | Physics and Astronomy
23.05.2017 | Life Sciences
23.05.2017 | Medical Engineering