Metal-Directed Protein Self-Assembly and Construction of Selective Metal Binding Sites in Protein-Protein Interfaces

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This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). This Research award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports work by Professor F. Akif Tezcan at the University of California, San Diego to carry out fundamental/basic studies on the self-assembly of supramolecular protein architectures directed by metal coordination. Nature uses Proteins as premier building blocks for sophisticated nanoscale architectures that carry out complex tasks and chemical transformations. Yet, the rational assembly of multi-protein complexes is an unmet challenge, because protein-protein interactions comprise an extensive set of weak, non-covalent bonds that are difficult targets for de novo design. In this research program, the strength, directionality and selectivity of metal-ligand interactions are exploited to control protein-protein interactions, thereby achieving specificity and affinity without requiring extensive and complementary binding surfaces. Such inorganic chemical control of protein-protein interactions is ultimately utilized towards the construction of functional, protein-based bioassemblies and novel metallocenters built within protein-protein interfaces. This trans-disciplinary program provides an effective platform for attracting members of underrepresented groups to research careers, mentoring and recruitment of transfer students who have a particularly hard time to adjust to the rigors of a large research university, and outreach to students in local high schools.The research under this award will pave the way for the future generation of stable, porous protein frameworks with reactive interfacial metal centers, biomaterials whose assembly/disassembly can be controlled by external stimuli, and provide fundamental information regarding the evolution of natural metalloproteins and enzymes.