Tight and specific lanthanide binding in a de novo TIM barrel with a large internal cavity designed by symmetric domain fusion
Abstract
Despite considerable advances in de novo protein design in recent years, it still remains challenging to engineer proteins with large internal cavities that can be functionalized to become biotechnological tools, such as specific binders, sensors, or catalysts. In this work, we outline a computational strategy to combine multiple de novo designed domains into symmetric protein assemblies that enclose large internal chambers. The high stability of de novo scaffolds enables ready functionalization of these chambers; for instance, with specific metal-binding sites, as demonstrated here by generating a lanthanide-binding protein with ultra-high affinity.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 17, 2020
- Source ID
- 10.1073/pnas.2008535117
Entities
People
- Cathleen Zeymer
- David Baker
- Donald Hilvert
- H Sebastian Sjöström
- Ian C Haydon
- Matthew J Bick
- Nikoletta Piperidou
- Po-Ssu Huang
- Shane J Caldwell
Organizations
- Canadian Institutes of Health Research
- Defense Threat Reduction Agency
- ETH Zurich
- Stanford University
- Swiss National Science Foundation
- Technical University of Munich
- University of Washington