Elaborating a coiled-coil-assembled octahedral protein cage with additional protein domains.

Autor: Cristie-David AS; Department of Chemistry, University of Michigan, Ann Arbor, Michigan, 48109., Koldewey P; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, 48109., Meinen BA; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, 48109., Bardwell JCA; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, 48109.; Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, 48109.; Howard Hughes Medical Institute, Chevy Chase, Maryland., Marsh ENG; Department of Chemistry, University of Michigan, Ann Arbor, Michigan, 48109.
Jazyk: angličtina
Zdroj: Protein science : a publication of the Protein Society [Protein Sci] 2018 Nov; Vol. 27 (11), pp. 1893-1900. Date of Electronic Publication: 2018 Oct 03.
DOI: 10.1002/pro.3497
Abstrakt: De novo design of protein nano-cages has potential applications in medicine, synthetic biology, and materials science. We recently developed a modular, symmetry-based strategy for protein assembly in which short, coiled-coil sequences mediate the assembly of a protein building block into a cage. The geometry of the cage is specified by the combination of rotational symmetries associated with the coiled-coil and protein building block. We have used this approach to design well-defined octahedral and tetrahedral cages. Here, we show that the cages can be further elaborated and functionalized by the addition of another protein domain to the free end of the coiled-coil: in this case by fusing maltose-binding protein to an octahedral protein cage to produce a structure with a designed molecular weight of ~1.8 MDa. Importantly, the addition of the maltose binding protein domain dramatically improved the efficiency of assembly, resulting in ~ 60-fold greater yield of purified protein compared to the original cage design. This study shows the potential of using small, coiled-coil motifs as off-the-shelf components to design MDa-sized protein cages to which additional structural or functional elements can be added in a modular manner.
(© 2018 The Protein Society.)
Databáze: MEDLINE
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