Controlled Protein Dimerization through Hybrid Coordination Motifs

Protein homodimerization is the simplest form of oligomerization that is frequently utilized for the construction of functional biological assemblies and the regulation of cellular pathways. Despite its simplicity, dimerization still poses an enormous challenge for protein engineering and chemical m...

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Veröffentlicht in:Inorganic chemistry 2010-05, Vol.49 (9), p.4362-4369
Hauptverfasser: Radford, Robert J, Nguyen, Phuong C, Ditri, Treffly B, Figueroa, Joshua S, Tezcan, F. Akif
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Sprache:eng
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Zusammenfassung:Protein homodimerization is the simplest form of oligomerization that is frequently utilized for the construction of functional biological assemblies and the regulation of cellular pathways. Despite its simplicity, dimerization still poses an enormous challenge for protein engineering and chemical maniupulation, owing to the large molecular surfaces involved in this process. We report here the construction of a hybrid coordination motifconsisting of a natural (His) and a non-natural ligand (quinolate)on the α-helical surface of cytochrome cb 562, which (a) simultaneously binds divalent metals with high affinity, (b) leads to a metal-induced increase in global protein stability, and importantly, (c) enables the formation of a discrete protein dimer, whose shape is dictated by the inner-sphere metal coordination geometry and closely approximates that of the DNA-binding domains of bZIP family transcription factors.
ISSN:0020-1669
1520-510X
DOI:10.1021/ic100534y