Filamentous actin (F-actin) forms many types of structures and dynamically regulates cell morphology and movement, and plays a mechanosensory role for extracellular stimuli. In this study, we determined that the smooth muscle-related transcription factor, cysteine-rich protein 2 (CRP2), regulates the supramolecular networks of F-actin. The structures of CRP2 and F-actin in solution were analyze...

Marine toxins targeting the actin cytoskeleton represent a new and promising class of anti-cancer compounds. Here we present a 2.0 A resolution structure of swinholide A, a marine macrolide, bound to two actin molecules. The structure demonstrates that the actin dimer in the complex does not represent a physiologically relevant entity, for the two actin molecules do not interact with each other...

Calpain 2 regulates membrane protrusion during cell migration. However, relevant substrates that mediate the effects of calpain on protrusion have not been identified. One potential candidate substrate is the actin binding protein cortactin. Cortactin is a Src substrate that drives actin polymerization by activating the Arp2/3 complex and also stabilizes the cortical actin network. We now provi...

Tropomyosin (Tm) is a coiled-coil protein that binds to filamentous actin (F-actin) and regulates its interactions with actin-binding proteins like myosin by moving between three positions on F-actin (the blocked, closed, and open positions). To elucidate the molecular details of Tm flexibility in relation to its binding to F-actin, we conducted extensive molecular dynamics simulations for both...

Filamentous actin and associated actin binding proteins play an essential role in governing the mechanical properties of eukaryotic cells. They can also play a critical role in disease; for example, mutations in α-actinin-4 (Actn4), a dynamic actin cross-linking protein, cause proteinuric disease in humans and mice. Amino acid substitutions strongly affect the binding affinity and protein struc...

Abstract CD157 is an ectoenzyme that has both cyclic ADP-ribose hydrolase and ADP-ribosyl cyclase activities. In the human hematopoietic system, prevalently expressed by cells of myelomonocytic lineage, interacts with extracellular matrix components regulates leukocyte diapedesis via integrin-mediated signaling. implicated in pathophysiology several neurological disorders. Although it lacks a c...