RT Journal Article
SR Electronic
T1 Dendrimer-like supramolecular assembly of proteins with a tunable size and valency through stepwise iterative growth
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.23.449676
DO 10.1101/2021.06.23.449676
A1 Jin-Ho Bae
A1 Hong-Sik Kim
A1 Gijeong Kim
A1 Ji-Joon Song
A1 Hak-Sung Kim
YR 2021
UL http://biorxiv.org/content/early/2021/06/24/2021.06.23.449676.abstract
AB The assembly of proteins in a programmable manner provides insight into the underlying mechanisms of protein self-assembly in nature as well as the creation of novel functional nanomaterials for practical applications. Despite many advances, however, a rational protein assembly with an easy scalability in terms of size and valency remains a challenging task. Here, we present a simple bottom-up approach to the supramolecular protein assembly with a tunable size and valency in a programmable manner. The dendrimer-like protein assembly, called a “prodrimer,” was constructed using a total of three monomeric proteins: a core and two building-block proteins. The prodrimer generations were grown by a stepwise and alternate addition of a building block using two pairs of orthogonal protein-peptide interactions, leading to a higher-generation prodrimer with a mega-dalton size and multi-valency. The valency of the prodrimers at the periphery was tunable with the generation, enabling a single-step functionalization. A second-generation prodrimer functionalized with a target-specific protein binder showed a three-order of magnitude increase in binding affinity compared to a monomeric counterpart due to the avidity. The prodrimers functionalized with a targeting moiety and a cytotoxic protein cargo exhibited a highly enhanced cellular cytotoxicity, exemplifying their utility as a protein delivery platform. The present approach can be effectively used in the creation of protein architectures with new functions for biotechnological and medical applications.Competing Interest StatementThe authors have declared no competing interest.