Spontaneous self-assembly of engineered armadillo repeat protein fragments into a folded structure.

Randall P Watson, Martin T Christen, Christina Ewald, Fabian Bumbak, Christian Reichen, Maja Mihajlovic, Elena Schmidt, Peter Güntert, Amedeo Caflisch, Andreas Plückthun, Oliver Zerbe

Structure (London, England : 1993) 2014 Jul 8

filter terms:

Repeat proteins are built of modules, each of which constitutes a structural motif. We have investigated whether fragments of a designed consensus armadillo repeat protein (ArmRP) recognize each other. We examined a split ArmRP consisting of an N-capping repeat (denoted Y), three internal repeats (M), and a C-capping repeat (A). We demonstrate that the C-terminal MA fragment adopts a fold similar to the corresponding part of the entire protein. In contrast, the N-terminal YM2 fragment constitutes a molten globule. The two fragments form a 1:1 YM2:MA complex with a nanomolar dissociation constant essentially identical to the crystal structure of the continuous YM3A protein. Molecular dynamics simulations show that the complex is structurally stable over a 1 μs timescale and reveal the importance of hydrophobic contacts across the interface. We propose that the existence of a stable complex recapitulates possible intermediates in the early evolution of these repeat proteins. Copyright © 2014 Elsevier Ltd. All rights reserved.

Citation

Randall P Watson, Martin T Christen, Christina Ewald, Fabian Bumbak, Christian Reichen, Maja Mihajlovic, Elena Schmidt, Peter Güntert, Amedeo Caflisch, Andreas Plückthun, Oliver Zerbe. Spontaneous self-assembly of engineered armadillo repeat protein fragments into a folded structure. Structure (London, England : 1993). 2014 Jul 8;22(7):985-95