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Publication Abstract from PubMed

Proteins forming the tegument layer of herpesviral virions mediate many essential processes in the viral replication cycle; yet, few have been characterized in detail. UL21 is one such multifunctional tegument protein, conserved among alphaherpesviruses. While it has been implicated in many processes in viral replication, ranging from nuclear egress to virion morphogenesis to cell-cell spread, its precise roles remain unclear. Here we report the 2.7-A crystal structure of the C-terminal domain of HSV-1 UL21 (UL21C) that has a unique alpha-helical fold resembling a dragonfly. Analysis of evolutionary conservation patterns and surface electrostatics pinpointed four regions of potential functional importance on the surface of UL21C to be pursued by mutagenesis. In combination with the previously determined structure of the N-terminal domain of UL21, the structure of UL21C provides a three-dimensional framework for a targeted exploration of the multiple roles of UL21 in replication and pathogenesis of alphaherpesviruses. Additionally, we describe an unanticipated ability of UL21 to bind RNA, which may hint at a yet unexplored function. IMPORTANCE: Due to limited genomic coding capacity of viruses, viral proteins are often multifunctional, which makes them attractive antiviral targets. Such multifunctionality, however, complicates their study, often done by constructing and characterizing null mutant viruses. A systematic exploration of these multifunctional proteins requires detailed roadmaps in the form of three-dimensional structures. In this work, we determined the crystal structure of the C-terminal domain of UL21, a multifunctional tegument protein conserved among alphaherpesviruses. Structural analysis pinpointed surface areas of potential functional importance that provide a starting point for mutagenesis. In addition, an unexpected RNA-binding ability of UL21 may expand its functional repertoire. The structure of UL21C and the observation of its RNA-binding ability are the latest additions to the navigational chart to guide the exploration of the multiple functions of UL21.

The novel structure and unexpected RNA-binding ability of the C-terminal domain of HSV-1 tegument protein UL21.,Metrick CM, Heldwein EE J Virol. 2016 Apr 6. pii: JVI.00475-16. PMID:27053559^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.