@article{5fc2bdfd0b8c46438116a3da186005dd,
title = "X-ray crystal structure and functional analysis of vaccinia virus K3L reveals molecular determinants for PKR subversion and substrate recognition",
abstract = "The vaccinia virus protein K3L subverts the mammalian antiviral defense mechanism by inhibiting the RNA-dependent protein kinase PKR. K3L is a structural mimic of PKR's natural substrate, the translation initiation factor eIF2α. To further our understanding of K3L inhibitory function and PKR substrate recognition, we have solved the 1.8 {\AA} X-ray crystal structure of K3L. The structure consists of a five-strand β barrel with an intervening helix insert region similar in topology to the functionally divergent S1 domain. Mutational analysis identifies two proximal regions of the K3L structure as possessing specialized PKR binding and inhibitory function. Further analysis reveals that PKR dimerization composes a key switch that regulates both its catalytic activation and its molecular recognition of K3L and eIF2α.",
author = "Dar, {Arvin C.} and Frank Sicheri",
note = "Funding Information: We thank Gerry Gish, Jun Liu, Joses Jones, Cheryl Arrowsmith, and Gwan-Su Yi for technical assistance with the K3L-PKR binding and K3L refolding experiments. We specially thank Glen Barber for helpful discussion and for providing PKR and K3L reagents that allowed us to initiate this project. We thank the BioCars staff at the Advanced Photon Source at Argonne National Laboratories, where diffraction data were collected. We thank Mike Tyers and Dan Durocher for helpful discussions during the preparation of this manuscript. This work was supported by grants from the National Cancer Institute of Canada. F.S. is a recipient of a National Cancer Institute of Canada Scientist award. ",
year = "2002",
month = aug,
doi = "10.1016/S1097-2765(02)00590-7",
language = "English",
volume = "10",
pages = "295--305",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "2",
}