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The molecular organization of cypovirus polyhedra


Cypoviruses and baculoviruses are notoriously difficult to eradicate because the virus particles are embedded in micrometre-sized protein crystals called polyhedra1,2. The remarkable stability of polyhedra means that, like bacterial spores, these insect viruses remain infectious for years in soil. The environmental persistence of polyhedra is the cause of significant losses in silkworm cocoon harvests but has also been exploited against pests in biological alternatives to chemical insecticides3,4. Although polyhedra have been extensively characterized since the early 1900s5, their atomic organization remains elusive6. Here we describe the 2 Å crystal structure of both recombinant and infectious silkworm cypovirus polyhedra determined using crystals 5–12 micrometres in diameter purified from insect cells. These are the smallest crystals yet used for de novo X-ray protein structure determination7. We found that polyhedra are made of trimers of the viral polyhedrin protein and contain nucleotides. Although the shape of these building blocks is reminiscent of some capsid trimers, polyhedrin has a new fold and has evolved to assemble in vivo into three-dimensional cubic crystals rather than icosahedral shells. The polyhedrin trimers are extensively cross-linked in polyhedra by non-covalent interactions and pack with an exquisite molecular complementarity similar to that of antigen–antibody complexes. The resulting ultrastable and sealed crystals shield the virus particles from environmental damage. The structure suggests that polyhedra can serve as the basis for the development of robust and versatile nanoparticles for biotechnological applications8 such as microarrays9 and biopesticides4.

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Figure 1: Compact trimers are the building blocks of polyhedra.
Figure 2: Polyhedra are built around a tight scaffold of H1 helices.
Figure 3: Polyhedra are dense and sealed microcrystals containing nucleotides.
Figure 4: Proposed mechanism for the release of virus particles.

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We are very grateful for support from E. N. Baker. We thank R. E. Thorne for providing MicroMesh mounts; J. Taylor, A. Mitra and colleagues at SBS for critically reading the manuscript; and M. Middleditch, C. Hobbis, R. Graves, R. Bunker, A. Wagner, E. Pohl and J. Diez for experimental help. S.G. is funded by the Swiss NCCR Structural Biology and E.C. by a TEAC Bright Futures doctoral scholarship. This work was supported by the NZ FRST (F.C.), the UARC (P.M.), the Maurice Wilkins Centre for Molecular Biodiscovery (E.C.) and grants for Regional Consortium Research Development Work from the Kansai Bureau of METI (K.I. and H.M.), from CREST by JST (H.M.) and a JSPS Invitation Fellowship for Research in Japan (P.M.).

Structures of polyhedrins from infectious, recombinant and kinase-containing polyhedra have been deposited in the Protein Data Bank with accession codes 2OH5, 2OH6 and 2OH7.

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Correspondence to Peter Metcalf.

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Coulibaly, F., Chiu, E., Ikeda, K. et al. The molecular organization of cypovirus polyhedra. Nature 446, 97–101 (2007).

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