TY  - JOUR
AU  - Gao, S
AU  - von der Malsburg, A.
AU  - Dick, A.
AU  - Faelber, K.
AU  - Schröder, G.F.
AU  - Haller, O.
AU  - Kochs, G.
AU  - Daumke, O.
TI  - Structure of Myxovirus Resistance Protein A Reveals Intra- and Intermolecular Domain Interactions Required for the Antiviral Function
JO  - Immunity
VL  - 35
SN  - 1074-7613
CY  - [Cambridge, Mass.]
PB  - Cell Press
M1  - PreJuSER-18855
SP  - 514 - 525
PY  - 2011
N1  - This project was supported by grants of the Deutsche Forschungsgemeinschaft (SFB 740/TP C7 and SFB958/A12 to O.D. and Ko1579/8-1 to G.K.), by a Career Development Fellowship of The International Human Frontier Science Program Organization, and by the EMBO Young Investigator Program to O.D. We are grateful to A. Brunger for providing us with the prerelease of CNS version 1.3, the BESSY staff at beamline BL14.1 and SLS staff at beamline X06SA for help with data collection, and S. Werner, S. Paeschke, and S. Gruber for technical assistance.
AB  - Human myxovirus resistance protein 1 (MxA) is an interferon-induced dynamin-like GTPase that acts as a cell-autonomous host restriction factor against many viral pathogens including influenza viruses. To study the molecular principles of its antiviral activity, we determined the crystal structure of nucleotide-free MxA, which showed an extended three-domain architecture. The central bundle signaling element (BSE) connected the amino-terminal GTPase domain with the stalk via two hinge regions. MxA oligomerized in the crystal via the stalk and the BSE, which in turn interacted with the stalk of the neighboring monomer. We demonstrated that the intra- and intermolecular domain interplay between the BSE and stalk was essential for oligomerization and the antiviral function of MxA. Based on these results, we propose a structural model for the mechano-chemical coupling in ring-like MxA oligomers as the principle mechanism for this unique antiviral effector protein.
KW  - Animals
KW  - Cell Line
KW  - Crystallography, X-Ray
KW  - GTP-Binding Proteins: chemistry
KW  - Humans
KW  - Models, Molecular
KW  - Protein Structure, Quaternary
KW  - Protein Structure, Tertiary
KW  - Structural Homology, Protein
KW  - myxovirus resistance proteins (NLM Chemicals)
KW  - GTP-Binding Proteins (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:21962493
UR  - <Go to ISI:>//WOS:000296657700011
DO  - DOI:10.1016/j.immuni.2011.07.012
UR  - https://juser.fz-juelich.de/record/18855
ER  -