De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy.
Abstract
Despite efforts for over 25 years, de novo protein design has not succeeded in achieving the TIM-barrel fold. Here we describe the computational design of four-fold symmetrical (β/α)8 barrels guided by geometrical and chemical principles. Experimental characterization of 33 designs revealed the importance of side chain-backbone hydrogen bonds for defining the strand register between repeat units. The X-ray crystal structure of a designed thermostable 184-residue protein is nearly identical to that of the designed TIM-barrel model. PSI-BLAST searches do not identify sequence similarities to known TIM-barrel proteins, and sensitive profile-profile searches indicate that the design sequence is distant from other naturally occurring TIM-barrel superfamilies, suggesting that Nature has sampled only a subset of the sequence space available to the TIM-barrel fold. The ability to design TIM barrels de novo opens new possibilities for custom-made enzymes.
Submission Details
ID: 42WeVJh83
Submitter: Connie Wang
Submission Date: July 31, 2017, 11:46 a.m.
Version: 1
Publication Details
Huang PS;Feldmeier K;Parmeggiani F;Velasco DAF;Höcker B;Baker D,Nat Chem Biol (2016) De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy. PMID:26595462Additional Information
Study Summary
| Number of data points | 29 |
| Proteins | Triosephosphate isomerase |
| Unique complexes | 29 |
| Assays/Quantities/Protocols | Experimental Assay: Tm |
| Libraries | De novo design of symmetric TIM-barrel proteins |
Structure view and single mutant data analysis
Study data
| Colors: | D | E | R | H | K | S | T | N | Q | A | V | I | L | M | F | Y | W | C | G | P |
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Data Distribution
Studies with similar sequences (approximate matches)