De novo design of a transmembrane Zn[superscript 2+]-transporting four-helix bundle
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 membrane-spanning, four-helical bundle that transports first-row transition metal ions Zn[superscript 2+] and Co[superscript 2+], but not...
| Main Authors: | , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Association for the Advancement of Science (AAAS)
2015
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| Online Access: | http://hdl.handle.net/1721.1/96253 https://orcid.org/0000-0002-1801-924X https://orcid.org/0000-0001-5255-5858 |
| Summary: | 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 membrane-spanning, four-helical bundle that transports first-row transition metal ions Zn[superscript 2+] and Co[superscript 2+], but not Ca[superscript 2+], 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 Zn[superscript 2+] ions diffuse down their concentration gradients, protons are antiported. These experiments illustrate the feasibility of designing membrane proteins with predefined structural and dynamic properties. |
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