3gjn
From Proteopedia
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===Following evolutionary paths to high affinity and selectivity protein-protein interactions using Colicin7 and Immunity proteins=== | ===Following evolutionary paths to high affinity and selectivity protein-protein interactions using Colicin7 and Immunity proteins=== | ||
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*[[Colicin Immunity Protein|Colicin Immunity Protein]] | *[[Colicin Immunity Protein|Colicin Immunity Protein]] | ||
*[[Directed evolution|Directed evolution]] | *[[Directed evolution|Directed evolution]] | ||
| + | *[[Mutant immunity protein 9 (variant R12-13)|Mutant immunity protein 9 (variant R12-13)]] | ||
| + | *[[Mutant immunity protein 9 (variant R12-2)|Mutant immunity protein 9 (variant R12-2)]] | ||
==Reference== | ==Reference== | ||
Revision as of 19:31, 25 July 2012
Contents |
Following evolutionary paths to high affinity and selectivity protein-protein interactions using Colicin7 and Immunity proteins
How do intricate multi-residue features such as protein-protein interfaces evolve? To address this question, we evolved a new colicin-immunity binding interaction. We started with Im9, which inhibits its cognate DNase ColE9 at 10(-14) M affinity, and evolved it toward ColE7, which it inhibits promiscuously (Kd > 10(-8) M). Iterative rounds of random mutagenesis and selection toward higher affinity for ColE7, and selectivity (against ColE9 inhibition), led to an approximately 10(5)-fold increase in affinity and a 10(8)-fold increase in selectivity. Analysis of intermediates along the evolved variants revealed that changes in the binding configuration of the Im protein uncovered a latent set of interactions, thus providing the key to the rapid divergence of new Im7 variants. Overall, protein-protein interfaces seem to share the evolvability features of enzymes, that is, the exploitation of promiscuous interactions and alternative binding configurations via 'generalist' intermediates, and the key role of compensatory stabilizing mutations in facilitating the divergence of new functions.
Following evolutionary paths to protein-protein interactions with high affinity and selectivity., Levin KB, Dym O, Albeck S, Magdassi S, Keeble AH, Kleanthous C, Tawfik DS, Nat Struct Mol Biol. 2009 Oct;16(10):1049-55. Epub 2009 Sep 13. PMID:19749752
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
3gjn is a 4 chain structure of Colicin and Colicin Immunity Protein with sequence from Escherichia coli. Full crystallographic information is available from OCA.
See Also
- Colicin
- Colicin Immunity Protein
- Directed evolution
- Mutant immunity protein 9 (variant R12-13)
- Mutant immunity protein 9 (variant R12-2)
Reference
- Levin KB, Dym O, Albeck S, Magdassi S, Keeble AH, Kleanthous C, Tawfik DS. Following evolutionary paths to protein-protein interactions with high affinity and selectivity. Nat Struct Mol Biol. 2009 Oct;16(10):1049-55. Epub 2009 Sep 13. PMID:19749752 doi:10.1038/nsmb.1670
