Cell Biology

Spinning a E4dly Weave

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Science  02 Nov 2012:
Vol. 338, Issue 6107, pp. 582
DOI: 10.1126/science.338.6107.582-a
CREDIT: H. D. OU ET AL., CELL 151, 304 (12 OCTOBER 2012) © 2012 ELSEVIER INC.

Adenovirus is a small DNA tumor virus. It expresses a number of “early” proteins during infection that take over the host cell for virus production by subverting cellular pathways. These early proteins are often quite small: E4-ORF3 is a mere 13 kD and yet can disrupt large protein complexes, interfere with tumor suppressors in a number of critical cellular pathways, and forms long cablelike structures in the host cell. Using super-resolution and electron microscopy, Ou et al. show that these cablelike assemblies appear to form a single continuous polymer with variable curvature and loops. This complex architecture requires nothing more than the E4 protein itself. The intricate “weave” of the polymer partitions the host cell nucleus into viral replication domains. The structure of a mutant form of the protein that forms dimers, rather than insoluble polymers, together with mutagenesis studies, suggest a model for polymer formation in which dimers can reciprocally or nonreciprocally domain-swap their C-terminal tails with other dimers. Glycine residues form a hinge allowing the C-terminal tail to adopt many different conformations that produce polymer branch points. Polymerization is required for E4 to target cellular tumor suppressors.

Cell 151, 304 (2012).

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