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Publication Abstract from PubMed

Metal coordination is a key structural and functional component of a large fraction of proteins. Given this dual role we considered the possibility that metal coordination may have played a templating role in the early evolution of protein folds and complexes. We describe here a rational design approach, Metal Templated Interface Redesign (MeTIR), that mimics the time course of a hypothetical evolutionary pathway for the formation of stable protein assemblies through an initial metal coordination event. Using a folded monomeric protein, cytochrome cb(562), as a building block we show that its non-self-associating surface can be made self-associating through a minimal number of mutations that enable Zn coordination. The protein interfaces in the resulting Zn-directed, D(2)-symmetrical tetramer are subsequently redesigned, yielding unique protein architectures that self-assemble in the presence or absence of metals. Aside from its evolutionary implications, MeTIR provides a route to engineer de novo protein interfaces and metal coordination environments that can be tuned through the extensive noncovalent bonding interactions in these interfaces.

Metal templated design of protein interfaces.,Salgado EN, Ambroggio XI, Brodin JD, Lewis RA, Kuhlman B, Tezcan FA Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):1827-32. Epub 2009 Dec 23. PMID:20080561^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.