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.
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
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine