TY - JOUR
T1 - Structure of IRF-3 Bound to the PRDIII-I Regulatory Element of the Human Interferon-β Enhancer
AU - Escalante, Carlos R.
AU - Nistal-Villán, Estanislao
AU - Shen, Leyi
AU - García-Sastre, Adolfo
AU - Aggarwal, Aneel K.
N1 - Funding Information:
We thank the staff at Advanced Photon Source (beamline 17ID) for facilitating X-ray data collection, Richard Cadagan for technical assistance, Luis Martinez-Sobrido for suggestions and plasmids, and Dimitris Thanos for discussions during the early stages of the project. This work was supported by grant AI41706 from the National Institutes of Health (NIH) (A.K.A) and by CIVIA, a human immunology center supported by NIH/NIAID U19 grant AI62623 (A.G.-S.).
PY - 2007/6/8
Y1 - 2007/6/8
N2 - Interferon regulatory factor 3 (IRF-3) is a key transcription factor in the assembly of the mammalian interferon-β (IFN-β) enhanceosome. We present here the structure of IRF-3 DNA binding domain in complex with the complete PRDIII-I regulatory element of the human IFN-β enhancer. We show that four IRF-3 molecules bind in tandem to, variably spaced, consensus and nonconsensus IRF sites on the composite element. The ability of IRF-3 to bind these variable sites derives in part from two nonconserved arginines (Arg78 and Arg86) that partake in alternate protein-DNA contacts. We also show that the protein-DNA contacts are highly overlapped and that all four IRF sites are required for gene activation in vivo. In addition, we show that changing the nonconsensus IRF sites to consensus sites creates a more efficient enhancer in vivo. Together, the structure and accompanying biological data provide insights into the assembly of the IFN-β enhanceosome in mammals.
AB - Interferon regulatory factor 3 (IRF-3) is a key transcription factor in the assembly of the mammalian interferon-β (IFN-β) enhanceosome. We present here the structure of IRF-3 DNA binding domain in complex with the complete PRDIII-I regulatory element of the human IFN-β enhancer. We show that four IRF-3 molecules bind in tandem to, variably spaced, consensus and nonconsensus IRF sites on the composite element. The ability of IRF-3 to bind these variable sites derives in part from two nonconserved arginines (Arg78 and Arg86) that partake in alternate protein-DNA contacts. We also show that the protein-DNA contacts are highly overlapped and that all four IRF sites are required for gene activation in vivo. In addition, we show that changing the nonconsensus IRF sites to consensus sites creates a more efficient enhancer in vivo. Together, the structure and accompanying biological data provide insights into the assembly of the IFN-β enhanceosome in mammals.
KW - DNA
UR - http://www.scopus.com/inward/record.url?scp=34249792638&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2007.04.022
DO - 10.1016/j.molcel.2007.04.022
M3 - Article
C2 - 17560375
AN - SCOPUS:34249792638
SN - 1097-2765
VL - 26
SP - 703
EP - 716
JO - Molecular Cell
JF - Molecular Cell
IS - 5
ER -