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
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction