5CWB: Crystal structure of de novo designed helical repeat protein DHR4

A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 degrees C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 A. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering.
PDB ID: 5CWBDownload
MMDB ID: 163335
PDB Deposition Date: 2015/7/27
Updated in MMDB: 2018/06
Experimental Method:
x-ray diffraction
Resolution: 1.55  Å
Source Organism:
Similar Structures:
Biological Unit for 5CWB: monomeric; determined by author and by software (PISA)
Molecular Components in 5CWB
Label Count Molecule
Protein (1 molecule)
Designed Helical Repeat Protein
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB