EMD-25579
D3-C3 computationally-designed rotor
EMD-25579
Single-particle10.2 Å
Deposition: 29/11/2021Map released: 02/02/2022
Last modified: 31/08/2022
Sample Organism:
Escherichia coli
Sample: D3-symmetric axel and C3-symmetric ring
Deposition Authors: Hansen JM, Courbet A
,
Quispe J ,
Kollman JM,
Baker D
Sample: D3-symmetric axel and C3-symmetric ring
Deposition Authors: Hansen JM, Courbet A
,
Quispe J ,
Kollman JM,
Baker D
Computational design of mechanically coupled axle-rotor protein assemblies.
Courbet A ,
Hansen J ,
Hsia Y ,
Bethel N ,
Park YJ ,
Xu C ,
Moyer A,
Boyken SE ,
Ueda G ,
Nattermann U ,
Nagarajan D ,
Silva DA ,
Sheffler W ,
Quispe J ,
Nord A ,
King N ,
Bradley P ,
Veesler D ,
Kollman J ,
Baker D
(2022) Science , 376 , 383 - 390
,
Hansen J ,
Hsia Y ,
Bethel N ,
Park YJ ,
Xu C ,
Moyer A,
Boyken SE ,
Ueda G ,
Nattermann U ,
Nagarajan D ,
Silva DA ,
Sheffler W ,
Quispe J ,
Nord A ,
King N ,
Bradley P ,
Veesler D ,
Kollman J ,
Baker D
(2022) Science , 376 , 383 - 390
Abstract:
Natural molecular machines contain protein components that undergo motion relative to each other. Designing such mechanically constrained nanoscale protein architectures with internal degrees of freedom is an outstanding challenge for computational protein design. Here we explore the de novo construction of protein machinery from designed axle and rotor components with internal cyclic or dihedral symmetry. We find that the axle-rotor systems assemble in vitro and in vivo as designed. Using cryo-electron microscopy, we find that these systems populate conformationally variable relative orientations reflecting the symmetry of the coupled components and the computationally designed interface energy landscape. These mechanical systems with internal degrees of freedom are a step toward the design of genetically encodable nanomachines.
Natural molecular machines contain protein components that undergo motion relative to each other. Designing such mechanically constrained nanoscale protein architectures with internal degrees of freedom is an outstanding challenge for computational protein design. Here we explore the de novo construction of protein machinery from designed axle and rotor components with internal cyclic or dihedral symmetry. We find that the axle-rotor systems assemble in vitro and in vivo as designed. Using cryo-electron microscopy, we find that these systems populate conformationally variable relative orientations reflecting the symmetry of the coupled components and the computationally designed interface energy landscape. These mechanical systems with internal degrees of freedom are a step toward the design of genetically encodable nanomachines.