De novo design of a transmembrane Zn[superscript 2+]-transporting four-helix bundle
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RockerRevision final MH.pdf
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Author(s)
Wang, Tuo
Hong, Mei
Joh, Nathan H.
Bhate, Manasi P.
Acharya, Rudresh
Wu, Yibing
Grabe, Michael
Grigoryan, Gevorg
DeGrado, William F.
Date Issued
December 2014
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Joh, N. H., T. Wang, M. P. Bhate, R. Acharya, Y. Wu, M. Grabe, M. Hong, G. Grigoryan, and W. F. DeGrado. “De Novo Design of a Transmembrane Zn2+-Transporting Four-Helix Bundle.” Science 346, no. 6216 (December 18, 2014): 1520–1524.
Version
Author's final manuscript
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 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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1126/science.1261172
