Modular repeat protein sculpting using rigid helical junctions.

摘要: The ability to precisely design large proteins with diverse shapes would enable applications ranging from the of protein binders that wrap around their target positioning multiple functional sites in specified orientations. We describe a backbone method for generating wide range rigid fusions between helix-containing and use it 75,000 structurally unique junctions monomeric homo-oligomeric de novo designed ankyrin repeat (RPs). Of junction designs were experimentally characterized, 82% have circular dichroism solution small-angle X-ray scattering profiles consistent models are stable at 95 °C. Crystal structures four close agreement rmsds 0.9 1.6 A. Electron microscopic images extended tetrameric ∼10-nm-diameter "L" "V" generated using models, demonstrating control provide shape sculpting over nanometer length scales.