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Precise assembly of complex beta sheet topologies from de novo designed building blocks.


ABSTRACT: Design of complex alpha-beta protein topologies poses a challenge because of the large number of alternative packing arrangements. A similar challenge presumably limited the emergence of large and complex protein topologies in evolution. Here, we demonstrate that protein topologies with six and seven-stranded beta sheets can be designed by insertion of one de novo designed beta sheet containing protein into another such that the two beta sheets are merged to form a single extended sheet, followed by amino acid sequence optimization at the newly formed strand-strand, strand-helix, and helix-helix interfaces. Crystal structures of two such designs closely match the computational design models. Searches for similar structures in the SCOP protein domain database yield only weak matches with different beta sheet connectivities. A similar beta sheet fusion mechanism may have contributed to the emergence of complex beta sheets during natural protein evolution.

SUBMITTER: King IC 

PROVIDER: S-EPMC4737653 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Precise assembly of complex beta sheet topologies from de novo designed building blocks.

King Indigo Chris IC   Gleixner James J   Doyle Lindsey L   Kuzin Alexandre A   Hunt John F JF   Xiao Rong R   Montelione Gaetano T GT   Stoddard Barry L BL   DiMaio Frank F   Baker David D  

eLife 20151209


Design of complex alpha-beta protein topologies poses a challenge because of the large number of alternative packing arrangements. A similar challenge presumably limited the emergence of large and complex protein topologies in evolution. Here, we demonstrate that protein topologies with six and seven-stranded beta sheets can be designed by insertion of one de novo designed beta sheet containing protein into another such that the two beta sheets are merged to form a single extended sheet, followe  ...[more]

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