PDBsum entry 5mfb

De novo protein

PDB id: 5mfb

Contents

Protein chains

238 a.a.

Waters ×69

PDB id:

5mfb

Name:

De novo protein

Title:

Designed armadillo repeat protein yiii(dq)4cqi

Structure:

Yiii(dq)4cqi. Chain: a, b. Engineered: yes

Source:

Synthetic construct. Organism_taxid: 32630. Expressed in: escherichia coli k-12. Expression_system_taxid: 83333

Resolution:

2.30Å R-factor: 0.187 R-free: 0.241

Authors:

S.Hansen,P.Ernst,C.Reichen,C.Ewald,P.Mittl,A.Plueckthun

Key ref:

S.Hansen et al. (2018). Curvature of designed armadillo repeat proteins allows modular peptide binding. J Struct Biol, 201, 108-117. PubMed id: 28864298 DOI: 10.1016/j.jsb.2017.08.009

Date:

18-Nov-16 Release date: 13-Sep-17

Protein chains

No UniProt id for this chain

Struc: 238 a.a.

DOI no: 10.1016/j.jsb.2017.08.009

J Struct Biol 201:108-117 (2018)

PubMed id: 28864298

Curvature of designed armadillo repeat proteins allows modular peptide binding.

S.Hansen, P.Ernst, S.L.B.König, C.Reichen, C.Ewald, D.Nettels, P.R.E.Mittl, B.Schuler, A.Plückthun.

ABSTRACT

Designed armadillo repeat proteins (dArmRPs) were developed to create a modular peptide binding technology where each of the structural repeats binds two residues of the target peptide. An essential prerequisite for such a technology is a dArmRP geometry that matches the peptide bond length. To this end, we determined a large set (n=27) of dArmRP X-ray structures, of which 12 were previously unpublished, to calculate curvature parameters that define their geometry. Our analysis shows that consensus dArmRPs exhibit curvatures close to the optimal range for modular peptide recognition. Binding of peptide ligands can induce a curvature within the desired range, as confirmed by single-molecule FRET experiments in solution. On the other hand, computationally designed ArmRPs, where side chains have been chosen with the intention to optimally fit into a geometrically optimized backbone, turned out to be more divergent in reality, and thus not suitable for continuous peptide binding. Furthermore, we show that the formation of a crystal lattice can induce small but significant deviations from the curvature adopted in solution, which can interfere with the evaluation of repeat protein scaffolds when high accuracy is required. This study corroborates the suitability of consensus dArmRPs as a scaffold for the development of modular peptide binders.