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TitleHierarchical design of pseudosymmetric protein nanocages.
Journal, issue, pagesNature, Year 2024
Publish dateDec 18, 2024
AuthorsQuinton M Dowling / Young-Jun Park / Chelsea N Fries / Neil C Gerstenmaier / Sebastian Ols / Erin C Yang / Adam J Wargacki / Annie Dosey / Yang Hsia / Rashmi Ravichandran / Carl D Walkey / Anika L Burrell / David Veesler / David Baker / Neil P King /
PubMed AbstractDiscrete protein assemblies ranging from hundreds of kilodaltons to hundreds of megadaltons in size are a ubiquitous feature of biological systems and perform highly specialized functions. Despite ...Discrete protein assemblies ranging from hundreds of kilodaltons to hundreds of megadaltons in size are a ubiquitous feature of biological systems and perform highly specialized functions. Despite remarkable recent progress in accurately designing new self-assembling proteins, the size and complexity of these assemblies has been limited by a reliance on strict symmetry. Here, inspired by the pseudosymmetry observed in bacterial microcompartments and viral capsids, we developed a hierarchical computational method for designing large pseudosymmetric self-assembling protein nanomaterials. We computationally designed pseudosymmetric heterooligomeric components and used them to create discrete, cage-like protein assemblies with icosahedral symmetry containing 240, 540 and 960 subunits. At 49, 71 and 96 nm diameter, these nanocages are the largest bounded computationally designed protein assemblies generated to date. More broadly, by moving beyond strict symmetry, our work substantially broadens the variety of self-assembling protein architectures that are accessible through design.
External linksNature / PubMed:39695230
MethodsEM (single particle)
Resolution3.1 - 14.9 Å
Structure data

EMDB-47034: Pseudosymmetric protein nanocages: GI4-F7 nanocage
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-47036, PDB-9dnd:
Pseudosymmetric protein nanocage GI4 -F7 (local refinement)
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-47037: Pseudosymmetric protein nanocage GI9-F7
Method: EM (single particle) / Resolution: 6.7 Å

EMDB-47038, PDB-9dne:
Pseudosymmetric protein nanocage GI9-F7 (local refinement)
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-47039: Pseudosymmetric protein nanocage GI16-F7
Method: EM (single particle) / Resolution: 14.9 Å

Source
  • synthetic construct (others)
KeywordsVIRAL PROTEIN / Fusion protein / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / pseudosymmetric protein nanocages

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