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3Q9U

In silico and in vitro co-evolution of a high affinity complementary protein-protein interface

Summary for 3Q9U
Entry DOI10.2210/pdb3q9u/pdb
Related3Q9N 3QA9 3q98
DescriptorCoA binding protein, consensus ankyrin repeat, COENZYME A (3 entities in total)
Functional Keywordsstructural genomics, israel structural proteomics center, ispc, prb-binding designed ankyrin repeat, protein binding, de novo protein
Biological sourceEscherichia coli
More
Total number of polymer chains4
Total formula weight66707.21
Authors
Primary citationKaranicolas, J.,Corn, J.E.,Chen, I.,Joachimiak, L.A.,Dym, O.,Peck, S.H.,Albeck, S.,Unger, T.,Hu, W.,Liu, G.,Delbecq, S.,Montelione, G.T.,Spiegel, C.P.,Liu, D.R.,Baker, D.
A de novo protein binding pair by computational design and directed evolution.
Mol.Cell, 42:250-260, 2011
Cited by
PubMed Abstract: The de novo design of protein-protein interfaces is a stringent test of our understanding of the principles underlying protein-protein interactions and would enable unique approaches to biological and medical challenges. Here we describe a motif-based method to computationally design protein-protein complexes with native-like interface composition and interaction density. Using this method we designed a pair of proteins, Prb and Pdar, that heterodimerize with a Kd of 130 nM, 1000-fold tighter than any previously designed de novo protein-protein complex. Directed evolution identified two point mutations that improve affinity to 180 pM. Crystal structures of an affinity-matured complex reveal binding is entirely through the designed interface residues. Surprisingly, in the in vitro evolved complex one of the partners is rotated 180° relative to the original design model, yet still maintains the central computationally designed hotspot interaction and preserves the character of many peripheral interactions. This work demonstrates that high-affinity protein interfaces can be created by designing complementary interaction surfaces on two noninteracting partners and underscores remaining challenges.
PubMed: 21458342
DOI: 10.1016/j.molcel.2011.03.010
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.3 Å)
Structure validation

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