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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
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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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