A designed protein interface that blocks fibril formation

Protein fibril formation is implicated in many diseases, and therefore much effort has been focused toward the development of inhibitors of this process. In a previous project, a monomeric protein was computationally engineered to bind itself and form a heterodimer complex following interfacial redesign. One of the protein monomers, termed monomer-B, was unintentionally destabilized and shown to form macroscopic fibrils. Interestingly, in the presence of the designed binding partner, fibril formation was blocked. Here we describe the complete characterization of the amyloid properties of monomer-B and the inhibition of fiber formation by the designed binding partner, monomer-A. Both proteins are mutants of the betal domain of streptococcal protein-G. The free monomer-B protein forms amyloid-type fibrils, as determined by transmission electron microscopy and the change in fluorescence of Thioflavin T, an amyloid-specific dye. Fibril formation kinetics are influenced by pH, protein concentration, and seeding with preformed fibrils. Under all conditions tested, monomer-A was able to inhibit the formation of monomer-B fibrils. This inhibition is specific to the engineered interaction, as incubation of monomer-B with wild-type protein-G (a structural homologue) did not result in inhibition under the same conditions. Thus, this de novo-designed heterodimeric complex is an excellent model system for the study of protein-based fibril formation and inhibition. This system provides additional insight into the development of pharmaceuticals for amyloid disorders, as well as the potential use of amyloid fibrils for self-assembling nanostructures

Next Generation NASA Hazard Detection System Development

The SPLICE project is continuing NASAs efforts to develop precision landing GN&C technologies for future lander missions. One of those technologies is the next generation Hazard Detection (HD) System, which consists of a new HD Lidar and HD Algorithms. The HD System is a modular system that will be adapted to meet specific mission needs in the future. This paper presents the design approach, the nominal concept of operations for which the first prototype is being designed, and the expected performance of the system

Effect of Processing Temperature on the Properties of a Polyvinyl Chloride Maxillofacial Elastomer

Mechanical properties and color of a plasticized polyvinyl chloride (PVC) maxillofacial elastomer were evaluated at processing temperatures from 140 to 190°C. The properties were dependent on processing temperature. Specimens prepared at 170°C had optimum mechanical properties with minimal discoloration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66749/2/10.1177_00220345830620102001.pd