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TitleBlueprinting expandable nanomaterials with standardized protein building blocks.
Journal, issue, pagesbioRxiv, Year 2023
Publish dateJun 9, 2023
PubMed AbstractA wooden house frame consists of many different lumber pieces, but because of the regularity of these building blocks, the structure can be designed using straightforward geometrical principles. The ...A wooden house frame consists of many different lumber pieces, but because of the regularity of these building blocks, the structure can be designed using straightforward geometrical principles. The design of multicomponent protein assemblies in comparison has been much more complex, largely due to the irregular shapes of protein structures . Here we describe extendable linear, curved, and angled protein building blocks, as well as inter-block interactions that conform to specified geometric standards; assemblies designed using these blocks inherit their extendability and regular interaction surfaces, enabling them to be expanded or contracted by varying the number of modules, and reinforced with secondary struts. Using X-ray crystallography and electron microscopy, we validate nanomaterial designs ranging from simple polygonal and circular oligomers that can be concentrically nested, up to large polyhedral nanocages and unbounded straight "train track" assemblies with reconfigurable sizes and geometries that can be readily blueprinted. Because of the complexity of protein structures and sequence-structure relationships, it has not been previously possible to build up large protein assemblies by deliberate placement of protein backbones onto a blank 3D canvas; the simplicity and geometric regularity of our design platform now enables construction of protein nanomaterials according to "back of an envelope" architectural blueprints.
External linksbioRxiv / PubMed:37333359 / PubMed Central
MethodsEM (single particle)
Resolution3.6 - 7.52 Å
Structure data

EMDB-29915: CryoEM map of a de novo designed octahedral nanocage with programmable volume; design cage_O4_34
Method: EM (single particle) / Resolution: 7.52 Å

EMDB-40070: Cryo-EM map of synthetic cage_O3_10 reconstructed without symmetry (C1)
Method: EM (single particle) / Resolution: 7.4 Å

EMDB-40071: Cryo-EM map of synthetic cage_O3_10 reconstructed with O symmetry
Method: EM (single particle) / Resolution: 6.0 Å

EMDB-40072: Cryo-EM map of synthetic cage_T3_5 reconstructed without symmetry (C1), with 1 trimer missing (class 3.1)
Method: EM (single particle) / Resolution: 6.5 Å

EMDB-40073: Cryo-EM map of synthetic cage_T3_5 reconstructed without symmetry (C1), with 1 monomer missing (class 3.0)
Method: EM (single particle) / Resolution: 6.1 Å

EMDB-40074: Cryo-EM map of synthetic cage_T3_5 reconstructed with T symmetry
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-40075: Cryo-EM map of synthetic cage_T3_5 reconstructed without symmetry (C1)
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-40076: Cryo-EM map of synthetic cage_T3_5+2 reconstructed without symmetry (C1)
Method: EM (single particle) / Resolution: 6.7 Å

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  • synthetic construct (others)

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