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1.D.139.  The Computationally Designed Transmembrane Protein Pore (CD-TMPP) Family  

The de novo design of stable, well-defined transmembrane protein pores that are capable of conducting ions selectively or are large enough to enable the passage of small-molecule fluorophores has been achieved (Xu et al. 2020). Thus, computational designed protein pores formed by two concentric rings of alpha-helices that are stable and monodisperse in both their water-soluble and their transmembrane forms has been reported by Xu et al. 2020. Crystal structures of the water-soluble forms of a 12-helical pore and a 16-helical pore closely match the computational design models. Patch-clamp electrophysiology experiments showed that the transmembrane form of the 12-helix pore enables the passage of ions across the membrane with high selectivity for potassium over sodium; ion passage is blocked by specific chemical modifications at the pore entrance. When incorporated into liposomes using in vitro protein synthesis, the transmembrane form of the 16-helix pore-but not the 12-helix pore enabled the passage of biotinylated Alexa Fluor 488. A cryo-EM structure of the 16-helix transmembrane pore closely matched the design model. The ability to produce structurally and functionally well-defined transmembrane pores opens the door to the creation of designer channels and pores for a wide variety of applications.

References associated with 1.D.139 family:

Xu, C., P. Lu, T.M. Gamal El-Din, X.Y. Pei, M.C. Johnson, A. Uyeda, M.J. Bick, Q. Xu, D. Jiang, H. Bai, G. Reggiano, Y. Hsia, T.J. Brunette, J. Dou, D. Ma, E.M. Lynch, S.E. Boyken, P.S. Huang, L. Stewart, F. DiMaio, J.M. Kollman, B.F. Luisi, T. Matsuura, W.A. Catterall, and D. Baker. (2020). Computational design of transmembrane pores. Nature 585: 129-134. 32848250