Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Computational design of transmembrane pores.
Journal, issue, pages	Nature, Vol. 585, Issue 7823, Page 129-134, Year 2020
Publish date	Aug 26, 2020
Authors	Chunfu Xu / Peilong Lu / Tamer M Gamal El-Din / Xue Y Pei / Matthew C Johnson / Atsuko Uyeda / Matthew J Bick / Qi Xu / Daohua Jiang / Hua Bai / Gabriella Reggiano / Yang Hsia / T J Brunette / Jiayi Dou / Dan Ma / Eric M Lynch / Scott E Boyken / Po-Ssu Huang / Lance Stewart / Frank DiMaio / Justin M Kollman / Ben F Luisi / Tomoaki Matsuura / William A Catterall / David Baker /
PubMed Abstract	Transmembrane channels and pores have key roles in fundamental biological processes and in biotechnological applications such as DNA nanopore sequencing, resulting in considerable interest in the ...Transmembrane channels and pores have key roles in fundamental biological processes and in biotechnological applications such as DNA nanopore sequencing, resulting in considerable interest in the design of pore-containing proteins. Synthetic amphiphilic peptides have been found to form ion channels, and there have been recent advances in de novo membrane protein design and in redesigning naturally occurring channel-containing proteins. However, 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 remains an outstanding challenge. Here we report the computational design of protein pores formed by two concentric rings of α-helices that are stable and monodisperse in both their water-soluble and their transmembrane forms. 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 show that, when expressed in insect cells, 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 modification 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-enables the passage of biotinylated Alexa Fluor 488. A cryo-electron microscopy structure of the 16-helix transmembrane pore closely matches 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.
External links	Nature / PubMed:32848250 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	2.4 - 7.6 Å
Structure data	20613 6u1s EMDB-20613, PDB-6u1s: Cryo-EM structure of a de novo designed 16-helix transmembrane nanopore, TMHC8_R. Method: EM (single particle) / Resolution: 7.6 Å 30126 6m6z EMDB-30126, PDB-6m6z: A de novo designed transmembrane nanopore, TMH4C4 Method: EM (single particle) / Resolution: 5.9 Å PDB-6o35: Crystal structure of a de novo designed octameric helical-bundle protein Method: X-RAY DIFFRACTION / Resolution: 2.4 Å PDB-6tj1: Crystal structure of a de novo designed hexameric helical-bundle protein Method: X-RAY DIFFRACTION / Resolution: 2.4 Å PDB-6tms: Crystal structure of a de novo designed hexameric helical-bundle protein Method: X-RAY DIFFRACTION / Resolution: 2.7 Å
Chemicals	ChemComp-HOH: WATER / Water ChemComp-SO4: SULFATE ION / Sulfate
Source	synthetic construct (others) escherichia coli (E. coli)
Keywords	DE NOVO PROTEIN / nanopore / de novo design / MEMBRANE PROTEIN / Helical bundle / octamer / computational design / pore / BIOSYNTHETIC PROTEIN / hexamer / computational protein design / Transmembrane / Rosetta