Linna An, Derrick R Hicks, Dmitri Zorine, Justas Dauparas, Basile I M Wicky, Lukas F Milles, Alexis Courbet, Asim K Bera, Hannah Nguyen, Alex Kang, Lauren Carter, David Baker
In pseudocyclic proteins, such as TIM barrels, β barrels, and some helical transmembrane channels, a single subunit is repeated in a cyclic pattern, giving rise to a central cavity that can serve as a pocket for ligand binding or enzymatic activity. Inspired by these proteins, we devised a deep-learning-based approach to broadly exploring the space of closed repeat proteins starting from only a specification of the repeat number and length. Biophysical data for 38 structurally diverse pseudocyclic designs produced in Escherichia coli are consistent with the design models, and the three crystal structures we were able to obtain are very close to the designed structures...
September 28, 2023: Nature Structural & Molecular Biology