@article{9fabccbd813f4befaeb649b8a18244cf,
title = "A structural basis for the assembly and functions of a viral polymer that inactivates multiple tumor suppressors",
abstract = "Evolution of minimal DNA tumor virus' genomes has selected for small viral oncoproteins that hijack critical cellular protein interaction networks. The structural basis for the multiple and dominant functions of adenovirus oncoproteins has remained elusive. E4-ORF3 forms a nuclear polymer and simultaneously inactivates p53, PML, TRIM24, and MRE11/RAD50/NBS1 (MRN) tumor suppressors. We identify oligomerization mutants and solve the crystal structure of E4-ORF3. E4-ORF3 forms a dimer with a central β core, and its structure is unrelated to known polymers or oncogenes. E4-ORF3 dimer units coassemble through reciprocal and nonreciprocal exchanges of their C-terminal tails. This results in linear and branched oligomer chains that further assemble in variable arrangements to form a polymer network that partitions the nuclear volume. E4-ORF3 assembly creates avidity-driven interactions with PML and an emergent MRN binding interface. This reveals an elegant structural solution whereby a small protein forms a multivalent matrix that traps disparate tumor suppressors. PaperFlick:",
author = "Ou, {Horng D.} and Witek Kwiatkowski and Deerinck, {Thomas J.} and Andrew Noske and Blain, {Katie Y.} and Land, {Hannah S.} and Conrado Soria and Powers, {Colin J.} and May, {Andrew P.} and Xiaokun Shu and Tsien, {Roger Y.} and Fitzpatrick, {James A.J.} and Long, {Jeff A.} and Ellisman, {Mark H.} and Senyon Choe and O'Shea, {Clodagh C.}",
note = "Funding Information: We thank F. McCormick, T. Hunter, J. Chory, V. Lundblad, J. Young, I. Verma, and members of the C.C.O. laboratory for all of their support, insights, and helpful comments. We thank S. Phan and M. Terada for help with EM tomography. This work was supported by the following NIH grants awarded to the Salk Institute: CA137094 to C.C.O., a T32 fellowship (CA009370) to H.D.O., P30CA014195 provides support for the Salk Cancer Center, P30NS057096 supports in part the Salk X-ray equipment. The National Center for Microscopy contributions were supported by NIH awards 5P41RR004050 and P41GM103412-24 to M.H.E. The MiniSOG probe development was supported under RO1GM086197 (to R.Y.T. and M.H.E.). C.C.O. is also supported by the William Scandling Developmental Chair and young investigator awards from the American Cancer Society, the Sontag Foundation, the Arnold and Mabel Beckman Foundation, and the Anna Fuller Fund. ",
year = "2012",
month = oct,
day = "12",
doi = "10.1016/j.cell.2012.08.035",
language = "English",
volume = "151",
pages = "304--319",
journal = "Cell",
issn = "0092-8674",
number = "2",
}