EFFECTS OF GLUTAMINES ON THE SELF-ASSEMBLY OF A BETA-HAIRPIN FIBRILS

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Amyloid fibrils, well-structured aggregates of misfolded protein, have been implicated in a number of prevalent human diseases such as Alzheimer's dementia and Creutzfeldt-Jacob's disease. While formed by a diverse repertoire of proteins and synthetic peptides, including many with glutamine-rich sequences, amyloid fibrils have a common cross-beta-structure. Even with this common arrangement and multiple models for the atomic structure of glutamine-rich amyloid, a dominant set of forces governing amyloid formation and stabilization have not been experimentally determined. Since the forces previously investigated have not included side-chain hydrogen bonding, we created a glutamine-rich model system by de novo design that is capable of these interactions. This model, in a disulfide-cyclized form, forms beta-sheet structures, as shown by circular dichroism, and exhibits a fibril morphology, as shown by atomic force microscopy.