Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Releasing the brakes

Two regulators of protein filament assembly use dramatically different—and competing—methods to inhibit a common target

Actin-based protein filaments participate in biological activities ranging from cell migration to muscle contraction. These filaments can be highly dynamic, with individual actin molecules spontaneously attaching to or dissociating from the ends of the fiber. Typically, however, such activity is closely regulated by factors like actin capping protein (CP).

Filaments exhibit physical polarity, with extension specifically occurring at the ‘barbed’ end, and CP inhibits addition of new actin molecules by firmly seating itself at this end. CP is widely conserved in species ranging from yeast to humans and acts a crucial regulator for a variety of actin-mediated cellular functions.

Accordingly, cells also produce factors that help remove CP from filament ends, such as the V-1 and CARMIL proteins. Yasushi Nitanai at the RIKEN SPring-8 Center in Harima recently partnered with Nagoya University researchers Shuichi Takeda and Yuichiro Maeda to characterize the mechanisms employed by these two CP regulators via structural analysis1.

CP is composed of an á and a â subunit, each of which has a projecting ‘tentacle’ domain. Previous work from Takeda and Maeda showed that CP relies on the á tentacle to latch onto actin while the â tentacle stabilizes the complex2. Their work with Nitanai has now demonstrated that V-1 acts as a direct counter to this process, binding the same portions of the á tentacle that mediate actin binding and thereby physically preventing them from associating with the filament.

Takeda and colleagues identified a markedly different mechanism for CARMIL, based on data that revealed a surprisingly dynamic structure for CP. “We had believed that CP was a rigid molecule, and never imagined that it was an intrinsically flexible molecule, continuously undergoing twisting motions,” says Takeda. CARMIL appears to actively exploit this flexibility, interacting with CP via a relatively unstructured domain. This association does not physically obstruct actin binding, but instead constrains CP into an arrangement that reduces its affinity for both the barbed end of actin filaments and the V-1 inhibitor.

The team’s results are in keeping with previous findings indicating that CARMIL can bind to CP that is already bound to filament ends and triggers its rapid dissociation. “We were impressed with the way that CARMIL utilizes the intrinsic fluctuation of CP to suppress capping activity,” says Takeda. In future studies, he and his colleagues hope to apply alternative structural biology techniques, such as nuclear magnetic resonance, to better capture the subtle details of the dynamic interactions between CARMIL, V-1 and CP.

The corresponding author for this highlight is based at the Structural Biophysics Laboratory, RIKEN SPring-8 Center

Journal information
1. 1.Takeda, S., Minakata, S., Koike, R., Kawahata, I., Narita, A., Kitazawa, M., Ota, M., Yamakuni, T., Maeda, Y. & Nitanai, Y. Two distinct mechanisms for actin capping protein regulation—steric and allosteric regulation. PLoS Biology 8, e1000416 (2010).

2. 2.Narita, A., Takeda, S., Yamashita, A. & Maeda, Y. Structural basis of actin filament capping at the barbed-end: a cryo-electron microscopy study. The EMBO Journal 25, 5626–5633 (2006).

gro-pr | Research asia research news
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

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...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

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...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

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...

Im Focus: New Products - Highlights of COMPAMED 2016

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...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'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...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>