6FES

Crystal structure of novel repeat protein BRIC2 fused to DARPin D12

Summary for 6FES

• Entry DOI: 10.2210/pdb6fes/pdb
• Descriptor: D12_BRIC2, a synthetic protein,D12_BRIC2, a synthetic protein, SULFATE ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: novel fold, computational design, corrugated repeat, de novo protein
• Biological source: synthetic construct; More
• Total number of polymer chains: 4
• Total formula weight: 165545.37

Authors

ElGamacy, M.,Coles, M.,Ernst, P.,Zhu, H.,Hartmann, M.D.,Plueckthun, A.,Lupas, A. (deposition date: 2018-01-03, release date: 2018-09-05, Last modification date: 2024-01-17)

Primary citation

ElGamacy, M.,Coles, M.,Ernst, P.,Zhu, H.,Hartmann, M.D.,Pluckthun, A.,Lupas, A.N.
An Interface-Driven Design Strategy Yields a Novel, Corrugated Protein Architecture.
ACS Synth Biol, 7:2226-2235, 2018

PubMed Abstract: Designing proteins with novel folds remains a major challenge, as the biophysical properties of the target fold are not known a priori and no sequence profile exists to describe its features. Therefore, most computational design efforts so far have been directed toward creating proteins that recapitulate existing folds. Here we present a strategy centered upon the design of novel intramolecular interfaces that enables the construction of a target fold from a set of starting fragments. This strategy effectively reduces the amount of computational sampling necessary to achieve an optimal sequence, without compromising the level of topological control. The solenoid architecture has been a target of extensive protein design efforts, as it provides a highly modular platform of low topological complexity. However, none of the previous efforts have attempted to depart from the natural form, which is characterized by a uniformly handed superhelical architecture. Here we aimed to design a more complex platform, abolishing the superhelicity by introducing internally alternating handedness, resulting in a novel, corrugated architecture. We employed our interface-driven strategy, designing three proteins and confirming the design by solving the structure of two examples.

PubMed: 30148951
DOI: 10.1021/acssynbio.8b00224

Experimental method

X-RAY DIFFRACTION (3 Å)