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TitleDynamic Assembly of Pentamer-Based Protein Nanotubes.
Journal, issue, pagesACS Nano, Vol. 19, Issue 9, Page 8786-8798, Year 2025
Publish dateMar 11, 2025
AuthorsLukasz Koziej / Farzad Fatehi / Marta Aleksejczuk / Matthew J Byrne / Jonathan G Heddle / Reidun Twarock / Yusuke Azuma /
PubMed AbstractHollow proteinaceous particles are useful nanometric containers for delivery and catalysis. Understanding the molecular mechanisms and the geometrical theory behind the polymorphic protein assemblies ...Hollow proteinaceous particles are useful nanometric containers for delivery and catalysis. Understanding the molecular mechanisms and the geometrical theory behind the polymorphic protein assemblies provides a basis for designing ones with the desired morphology. As such, we found that a circularly permuted variant of a cage-forming enzyme, lumazine synthase, cpAaLS, assembles into a variety of hollow spherical and cylindrical structures in response to changes in ionic strength. Cryogenic electron microscopy revealed that these structures are composed entirely of pentameric subunits, and the dramatic cage-to-tube transformation is attributed to the moderately hindered 3-fold symmetry interaction and the imparted torsion angle of the building blocks, where both mechanisms are mediated by an α-helix domain that is untethered from the native position by circular permutation. Mathematical modeling suggests that the unique double- and triple-stranded helical arrangements of subunits are optimal tiling patterns, while different geometries should be possible by modulating the interaction angles of the pentagons. These structural insights into dynamic, pentamer-based protein cages and nanotubes afford guidelines for designing nanoarchitectures with customized morphology and assembly characteristics.
External linksACS Nano / PubMed:39993171 / PubMed Central
MethodsEM (helical sym.) / EM (single particle)
Resolution2.08 - 3.1 Å
Structure data

50999

9g3h

EMDB-50999, PDB-9g3h:
Circularly permuted lumazine synthase twisted tube with no gap between between double strands
Method: EM (helical sym.) / Resolution: 2.44 Å

51000

9g3i

EMDB-51000, PDB-9g3i:
Circularly permuted lumazine synthase twisted tube with 18 Angstrom gap between double strands
Method: EM (helical sym.) / Resolution: 2.85 Å

51001

9g3j

EMDB-51001, PDB-9g3j:
Circularly permuted lumazine synthase twisted tube with 28 Angstrom gap between double strands
Method: EM (helical sym.) / Resolution: 3.1 Å

51003

9g3m

EMDB-51003, PDB-9g3m:
Circularly permuted lumazine synthase triple-stranded straight tube
Method: EM (helical sym.) / Resolution: 3.09 Å

51004

9g3n

EMDB-51004, PDB-9g3n:
Circularly permuted lumazine synthase 36-pentamer spherical cage
Method: EM (single particle) / Resolution: 3.07 Å

51005

9g3o

EMDB-51005, PDB-9g3o:
Circularly permuted lumazine synthase 24-pentamer spherical cage
Method: EM (single particle) / Resolution: 2.76 Å

51006

9g3p

EMDB-51006, PDB-9g3p:
Circularly permuted lumazine synthase 12-pentamer spherical cage
Method: EM (single particle) / Resolution: 2.08 Å

Source
  • aquifex aeolicus vf5 (bacteria)
KeywordsDE NOVO PROTEIN / protein cage / protein engineering / self-assembly / geometry / helical reconstruction / bionanotechnology / polymorphism / pentamer

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