A Flexible Symmetry-Based Approach to Assembling Protein Nano-Cages
Abstract
The objective of the research effort is to develop a novel and highly generalizable strategy for the assembly of proteins into geometrically well-defined, nanoscale structures with cage-like topologies. The research effort will encompass three aims: Aim 1: Further Characterization and Refinement of Nano-cage Design Proof-of-concept studies provide excellent support for the feasibility of the symmetry-based nano-cage design strategy. However, there are still aspects of the design that remain to be understand and refined. This aim will explore possible heterogeneity in the orientations of the building block protein and coiled-coil domains with respect to the inside and outside of the cage, approaches to improve the efficiency of the assembly process, and strategies to prevent the formation of off-target oligomeric species. Aim 2: Extension of the Design Strategy to Construct Proteins with Other Geometries The symmetry-based design strategy has successfully been used to assemble octahedral and tetrahedral cage geometries, and proof-of-concept studies indicate that the spacer length connecting the coiled-coil and building block protein is the most important parameter that needs to be optimized for efficient assembly. Building on these results, the goal of this aim is to demonstrate that the design strategy can be generalized to include proteins with other quaternary structures. First, an icosahedral cage will be assembled from the same trimeric esterase employed for the construction of the octahedral and tetrahedral cages. To further establish the generality of the design approach, protein cages will be assembled using proteins with different quaternary structures (dimeric, tetrameric, pentameric) that will be combined with 3-stranded, 4-stranded or 5-stranded coiled-coils. Aim 3: Strategies for Controlling Nano-cage Assembly A unique feature of the symmetry-based design strategy is the potential to use the coiled-coil domains to make cage assembly/disassembly responsive to environmental triggers. Experiments in this aim will investigate whether nano-cage assembly can be designed to be pH-dependent or redox-dependent.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 12, 2017
- Source ID
- W911NF1610147
Entities
People
- Neil Marsh
Organizations
- Army Contracting Command
- United States Army
- University of Michigan