De novo design of tunable, pH-driven conformational changes


After implementing many upgrades made possible by IDAT support, the SIBYLS beamline has enabled the collection of data for over 50 laboratories in 2019 (so far). High impact results have begun to be reported in journals using the new high throughput and size exclusion coupled SAXS (HT and SEC-SAXS) capabilities. Representative results include those from the Baker laboratory at University of Washington. The Baker laboratory is the leading de-novo protein design laboratory in the world and relies heavily on SAXS capabilities provided through IDAT funding. Results will undoubtedly impact synthetic biology projects of relevance to DOE-BER. In addition, DOE seeks to leverage scientific scale to accomplish missions that could not be accomplished by single PI laboratories.

Recently in Science:

De novo design_baker Paper.png

Environmentally triggered conformational changes can now be programmed by de novo protein design as shown through SAXS data collected at the SIBYLS beam line 12.3.1 with IDAT support. The ability of naturally occurring proteins to change conformation in response to environmental changes is critical to biological function. The Baker lab designed homotrimers and heterodimers that are stable above pH 6.5 but undergo cooperative, large-scale conformational changes when the pH is lowered upon disassembly, the designed proteins disrupt lipid membranes both in vitro and after being endocytosed in mammalian cells.

Read more about it here:

Scott E. Boyken, Mark A. Benhaim, Florian Busch, Mengxuan Jia, Heejun Choi, Jason C. Klima, Zibo Chen, Carl Walkey, Alexander mileant, Aniruddha Sahasrabuddhe, Kathry Y. Wei, Edgar A Hodge, Sarah Byron, Alfredo Quijano-Rubio, Banumathi Sankaran, NeilP king, Jennifer Lippincott-Schwartz, Vicki H. Wysocki, Kelly K. Lee, David Baker De novo design of tunable, pH-driven conformational changes Science 17 May 2019: Vol. 364, Issue 6441, pp. 658-664 DOI: 10.1126/science.aav7897

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