dc.contributor.author | Wang, Tuo | |
dc.contributor.author | Hong, Mei | |
dc.contributor.author | Joh, Nathan H. | |
dc.contributor.author | Bhate, Manasi P. | |
dc.contributor.author | Acharya, Rudresh | |
dc.contributor.author | Wu, Yibing | |
dc.contributor.author | Grabe, Michael | |
dc.contributor.author | Grigoryan, Gevorg | |
dc.contributor.author | DeGrado, William F. | |
dc.date.accessioned | 2015-03-30T17:33:10Z | |
dc.date.available | 2015-03-30T17:33:10Z | |
dc.date.issued | 2014-12 | |
dc.date.submitted | 2014-09 | |
dc.identifier.issn | 0036-8075 | |
dc.identifier.issn | 1095-9203 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/96253 | |
dc.description.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. | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (R01 GM088204) | en_US |
dc.language.iso | en_US | |
dc.publisher | American Association for the Advancement of Science (AAAS) | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1126/science.1261172 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | en_US |
dc.source | Prof. Hong via Erja Kajosalo | en_US |
dc.title | De novo design of a transmembrane Zn[superscript 2+]-transporting four-helix bundle | en_US |
dc.type | Article | en_US |
dc.identifier.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. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemistry | en_US |
dc.contributor.mitauthor | Hong, Mei | en_US |
dc.contributor.mitauthor | Wang, Tuo | en_US |
dc.relation.journal | Science | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Joh, N. H.; Wang, T.; Bhate, M. P.; Acharya, R.; Wu, Y.; Grabe, M.; Hong, M.; Grigoryan, G.; DeGrado, W. F. | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-1801-924X | |
dc.identifier.orcid | https://orcid.org/0000-0001-5255-5858 | |
mit.license | OPEN_ACCESS_POLICY | en_US |
mit.metadata.status | Complete | |