TY - JOUR
T1 - Stimulus-responsive self-assembly of protein-based fractals by computational design
AU - Hernández, Nancy E.
AU - Hansen, William A.
AU - Zhu, Denzel
AU - Shea, Maria E.
AU - Khalid, Marium
AU - Manichev, Viacheslav
AU - Putnins, Matthew
AU - Chen, Muyuan
AU - Dodge, Anthony G.
AU - Yang, Lu
AU - Marrero-Berríos, Ileana
AU - Banal, Melissa
AU - Rechani, Phillip
AU - Gustafsson, Torgny
AU - Feldman, Leonard C.
AU - Lee, Sang Hyuk
AU - Wackett, Lawrence P.
AU - Dai, Wei
AU - Khare, Sagar D.
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Fractal topologies, which are statistically self-similar over multiple length scales, are pervasive in nature. The recurrence of patterns in fractal-shaped branched objects, such as trees, lungs and sponges, results in a high surface area to volume ratio, which provides key functional advantages including molecular trapping and exchange. Mimicking these topologies in designed protein-based assemblies could provide access to functional biomaterials. Here we describe a computational design approach for the reversible self-assembly of proteins into tunable supramolecular fractal-like topologies in response to phosphorylation. Guided by atomic-resolution models, we develop fusions of Src homology 2 (SH2) domain or a phosphorylatable SH2-binding peptide, respectively, to two symmetric, homo-oligomeric proteins. Mixing the two designed components resulted in a variety of dendritic, hyperbranched and sponge-like topologies that are phosphorylation-dependent and self-similar over three decades (~10 nm–10 μm) of length scale, in agreement with models from multiscale computational simulations. Designed assemblies perform efficient phosphorylation-dependent capture and release of cargo proteins.
AB - Fractal topologies, which are statistically self-similar over multiple length scales, are pervasive in nature. The recurrence of patterns in fractal-shaped branched objects, such as trees, lungs and sponges, results in a high surface area to volume ratio, which provides key functional advantages including molecular trapping and exchange. Mimicking these topologies in designed protein-based assemblies could provide access to functional biomaterials. Here we describe a computational design approach for the reversible self-assembly of proteins into tunable supramolecular fractal-like topologies in response to phosphorylation. Guided by atomic-resolution models, we develop fusions of Src homology 2 (SH2) domain or a phosphorylatable SH2-binding peptide, respectively, to two symmetric, homo-oligomeric proteins. Mixing the two designed components resulted in a variety of dendritic, hyperbranched and sponge-like topologies that are phosphorylation-dependent and self-similar over three decades (~10 nm–10 μm) of length scale, in agreement with models from multiscale computational simulations. Designed assemblies perform efficient phosphorylation-dependent capture and release of cargo proteins.
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U2 - 10.1038/s41557-019-0277-y
DO - 10.1038/s41557-019-0277-y
M3 - Article
C2 - 31209296
AN - SCOPUS:85067657324
SN - 1755-4330
VL - 11
SP - 605
EP - 614
JO - Nature Chemistry
JF - Nature Chemistry
IS - 7
ER -