Title

De novo design of a transmembrane zn2+-transporting four-helix bundle

Document Type

Article

Publication Date

12-19-2014

Abstract

The design of functional membrane proteins from first principles represents a grand challenge in chemistry and structural biology. Here, we report the design of a membranespanning, four-helical bundle that transports first-row transition metal ions Zn 2+ and Co2+, but not Ca2+, across membranes. The conduction path was designed to contain two di-metal binding sites that bind with negative cooperativity. X-ray crystallography and solid-state and solution nuclear magnetic resonance indicate that the overall helical bundle is formed from two tightly interacting pairs of helices, which form individual domains that interact weakly along a more dynamic interface. Vesicle flux experiments show that as Zn2+ ions diffuse down their concentration gradients, protons are antiported. These experiments illustrate the feasibility of designing membrane proteins with predefined structural and dynamic properties.

Publication Source (Journal or Book title)

Science

First Page

1520

Last Page

1524

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