Structure of EPCR in a non-canonical conformation

Structural motion and conformational flexibility are often linked to biological functions of proteins. Whether the endothelial protein C receptor (EPCR), like other molecules, is vulnerable to folding transitions or might adopt alternative conformations remains unknown. The current understanding points to a rigid molecular structure suitable for binding of its ligands, like the anticoagulant protein C, or the CIDRα1 domains of Plasmodium falciparum. In this study, we have identified a novel conformation of EPCR, captured by X-ray diffraction analyses, whereby Tyr154 shows a dramatically altered structural arrangement, likely incompatible with protein C binding. Biolayer interferometry analysis confirms previous results supporting a critical role for this position in protein C binding. Importantly, the conformational change has no apparent effect in the bound lipid. We conclude these findings reveal a site of conformational vulnerability in EPCR and inform a highly malleable region that could modulate EPCR functions.

A Numerically Scaled Spring-Friction System and Validation by Shaking Table Test

The seismic isolation efficiency of different friction-based devices needs verification by shaking table test, but faces problems in scaling before the test due to their frictional nonlinearity. To solve the scaling problems, a simplified civil structure, isolated by a self-centering spring-friction device, was numerically scaled in different ways considering the effect of friction action. The seismic responses of the scaled models were scaled back to those of the prototype and compared with the seismic responses of the prototype. The scaling problems and solutions were validated by a shaking table test on simply supported bridges using friction pendulum bearings (FPBs). The results show that both the unscaled gravity on a shaking table and the unscaled non-uniform friction distribution cause an inaccurate friction force in the structural motion equations of scaled models, and thus causing the scaling errors. One new and valid solution, i.e. changing the friction coefficient and scaling the non-uniform friction distribution to keep an accurate friction force for the scaled models, is put forward to avoid the scaling errors thoroughly. Another new solution shows that an increasing peak ground acceleration (PGA) can increase the other forces, while weakening the ratio of inaccurate friction force in the structural motion equations of the scaled models, which therefore reducing the scaling errors of acceleration and relative displacement responses, but not the scaling errors of residual displacement responses. In addition, the time-varying friction, the interface separation and collision of bearings, and other complex factors are found to cause scaling errors and need further investigation.

The crystal structure of AjiA1 reveals a novel structural motion mechanism in the adenylate-forming enzyme family

Adenylate-forming enzymes (AFEs) are a mechanistic superfamily of proteins that are involved in many cellular roles. In the biosynthesis of benzoxazole antibiotics, an AFE has been reported to play a key role in the condensation of cyclic molecules. In the biosynthetic gene cluster for the benzoxazole AJI9561, AjiA1 catalyzes the condensation of two 3-hydroxyanthranilic acid (3-HAA) molecules using ATP as a co-substrate. Here, the enzymatic activity of AjiA1 is reported together with a structural analysis of its apo form. The structure of AjiA1 was solved at 2.0 Å resolution and shows a conserved fold with other AFE family members. AjiA1 exhibits activity in the presence of 3-HAA (K m = 77.86 ± 28.36, k cat = 0.04 ± 0.004) and also with the alternative substrate 3-hydroxybenzoic acid (3-HBA; K m = 22.12 ± 31.35, k cat = 0.08 ± 0.005). The structure of AjiA1 in the apo form also reveals crucial conformational changes that occur during the catalytic cycle of this enzyme which have not been described for any other AFE member. Consequently, the results shown here provide insights into this protein family and a new subgroup is proposed for enzymes that are involved in benzoxazole-ring formation.

Three-dimensional FSI Simulation by Using a Novel Hybrid Scaling – Application to the Tacoma Narrows Bridge

In this paper a novel fluid-structure interaction approach for simulating flutter phenomenon is presented. The method is capable of modelling the structural motion and the fluid flow coupling in a fully three-dimensional manner. The key step of the proposed FSI procedure is a hybrid scaling of the physical fields; certain properties of the CFD simulation are scaled, while those of the mechanical system are kept original. This kind of scaling provides a significant speedup, since the number of the costly CFD time steps can be remarkably reduced. The acceptable computational time makes it possible to consider complex engineering problems such as buffeting, vortex shedding or flutter of a bridge deck or a wing of an airplane.

Series-Type Pendulum Tuned Mass Damper-Tuned Sloshing Damper

A pendulum-type tuned mass damper (TMD)-tuned sloshing damper (TSD) system is proposed as a cost-effective device to reduce wind-induced structural motion. Lagrange's principle is employed to develop an equivalent mechanical model for the system. The sloshing liquid provides additional gravitational restoring force to the pendulum TMD but does not provide a corresponding increase to its inertia. As a result, the natural frequency of the pendulum TMD is increased due to the TSD degree-of-freedom. Shake table testing is conducted on several pendulum TMD-TSD systems that are subjected to harmonic base excitation at discrete frequencies near the natural frequency of the pendulum TMD. The modeled and experimental results are in reasonable agreement when the liquid is not shallow or the response amplitude is not large. The pendulum TMD-TSD is coupled to a linear structure, and it is demonstrated through an analytical study that the device provides performance that is comparable to a traditional TMD. The proposed system is advantageous because it does not require a viscous damping system that is often one of the most costly components of traditional TMDs.