The Structure of Mouse Cytomegalovirus m04 Protein Obtained from Sparse NMR Data Reveals a Conserved Fold of the m02-m06 Viral Immune Modulator Family
Publication date: Available online 7 August 2014
Source:Structure
Author(s): Nikolaos*G. Sgourakis , Kannan Natarajan , Jinfa Ying , Beat Vogeli , Lisa*F. Boyd , David*H. Margulies , Ad Bax
Immunoevasins are key proteins used by viruses to subvert host immune responses. Determining their high-resolution structures is key to understanding virus-host interactions toward the design of vaccines and other antiviral therapies. Mouse cytomegalovirus encodes a unique set of immunoevasins, the m02-m06 family, that modulates major histocompatibility complex class I (MHC-I) antigen presentation to CD8+ T*cells and natural killer cells. Notwithstanding the large number of genetic and functional studies, the structural biology of immunoevasins remains incompletely understood, largely because of crystallization bottlenecks. Here we implement a*technology using sparse nuclear magnetic resonance data and integrative Rosetta modeling to determine the structure of the m04/gp34 immunoevasin extracellular domain. The structure reveals a ? fold that is representative of the m02-m06 family of viral proteins, several of which are known to bind MHC-I molecules and interfere with antigen presentation, suggesting its role as a diversified immune regulation module.
Graphical abstract
Teaser
Sgourakis et*al. describe a hybrid approach for determining the structure of proteins using sparse NMR datasets coupled with
molecular modeling. Using this new approach, the structure of a viral protein has been determined to high precision, a first step in understanding the molecular basis of its function.
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