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
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Physics and Astronomy
24.03.2017 | Materials Sciences
24.03.2017 | Health and Medicine