%0 Journal Article %1 Lu2018DesignedTransmembraneProteins %A Lu, Peilong %A Min, Duyoung %A DiMaio, Frank %A Wei, Kathy Y. %A Vahey, Michael D. %A Boyken, Scott E. %A Chen, Zibo %A Fallas, Jorge A. %A Ueda, George %A Sheffler, William %A Mulligan, Vikram Khipple %A Xu, Wenqing %A Bowie, James U. %A Baker, David %D 2018 %I American Association for the Advancement of Science %J Science %K biological-engineering macromolecular-engineering protein-design %N 6379 %P 1042--1046 %R 10.1126/science.aaq1739 %T Accurate computational design of multipass transmembrane proteins %U http://science.sciencemag.org/content/359/6379/1042 %V 359 %X In recent years, soluble protein design has achieved successes such as artificial enzymes and large protein cages. Membrane proteins present a considerable design challenge, but here too there have been advances, including the design of a zinc-transporting tetramer. Lu et al. report the design of stable transmembrane monomers, homodimers, trimers, and tetramers with up to eight membrane-spanning regions in an oligomer. The designed proteins adopted the target oligomerization state and localized to the predicted cellular membranes, and crystal structures of the designed dimer and tetramer reflected the design models.Science, this issue p. 1042The computational design of transmembrane proteins with more than one membrane-spanning region remains a major challenge. We report the design of transmembrane monomers, homodimers, trimers, and tetramers with 76 to 215 residue subunits containing two to four membrane-spanning regions and up to 860 total residues that adopt the target oligomerization state in detergent solution. The designed proteins localize to the plasma membrane in bacteria and in mammalian cells, and magnetic tweezer unfolding experiments in the membrane indicate that they are very stable. Crystal structures of the designed dimer and tetramer—a rocket-shaped structure with a wide cytoplasmic base that funnels into eight transmembrane helices—are very close to the design models. Our results pave the way for the design of multispan membrane proteins with new functions.

@article{Lu2018DesignedTransmembraneProteins, abstract = {In recent years, soluble protein design has achieved successes such as artificial enzymes and large protein cages. Membrane proteins present a considerable design challenge, but here too there have been advances, including the design of a zinc-transporting tetramer. Lu et al. report the design of stable transmembrane monomers, homodimers, trimers, and tetramers with up to eight membrane-spanning regions in an oligomer. The designed proteins adopted the target oligomerization state and localized to the predicted cellular membranes, and crystal structures of the designed dimer and tetramer reflected the design models.Science, this issue p. 1042The computational design of transmembrane proteins with more than one membrane-spanning region remains a major challenge. We report the design of transmembrane monomers, homodimers, trimers, and tetramers with 76 to 215 residue subunits containing two to four membrane-spanning regions and up to 860 total residues that adopt the target oligomerization state in detergent solution. The designed proteins localize to the plasma membrane in bacteria and in mammalian cells, and magnetic tweezer unfolding experiments in the membrane indicate that they are very stable. Crystal structures of the designed dimer and tetramer{\textemdash}a rocket-shaped structure with a wide cytoplasmic base that funnels into eight transmembrane helices{\textemdash}are very close to the design models. Our results pave the way for the design of multispan membrane proteins with new functions.}, added-at = {2018-03-05T19:47:51.000+0100}, author = {Lu, Peilong and Min, Duyoung and DiMaio, Frank and Wei, Kathy Y. and Vahey, Michael D. and Boyken, Scott E. and Chen, Zibo and Fallas, Jorge A. and Ueda, George and Sheffler, William and Mulligan, Vikram Khipple and Xu, Wenqing and Bowie, James U. and Baker, David}, biburl = {https://www.bibsonomy.org/bibtex/2911cce48c10d635140b0bc560d71b103/salotz}, description = {Accurate computational design of multipass transmembrane proteins | Science}, doi = {10.1126/science.aaq1739}, eprint = {http://science.sciencemag.org/content/359/6379/1042.full.pdf}, interhash = {eac6e1e8360b9e96021afed4bb73016e}, intrahash = {911cce48c10d635140b0bc560d71b103}, issn = {0036-8075}, journal = {Science}, keywords = {biological-engineering macromolecular-engineering protein-design}, number = 6379, pages = {1042--1046}, publisher = {American Association for the Advancement of Science}, timestamp = {2018-03-05T19:47:51.000+0100}, title = {Accurate computational design of multipass transmembrane proteins}, url = {http://science.sciencemag.org/content/359/6379/1042}, volume = 359, year = 2018 }