4k70 | pdb_00004k70
Crystal Structure of N-terminal half of Pseudorabiesvirus UL37 protein
Structural highlights
FunctionPublication Abstract from PubMedIn cells infected with herpesviruses, two capsid-associated, or inner-tegument, proteins UL37 and UL36 control cytosolic trafficking of capsids by as yet poorly understood mechanisms. Here, we report the crystal structure of the N-terminal half of UL37 from pseudorabies virus, an alphaherpesvirus closely related to herpes simplex viruses and varicella-zoster virus. The structure - the first for any alphaherpesvirus inner tegument protein - reveals an elongated molecule of a complex architecture, rich in helical bundles. To explore the function of UL37 N terminus, we used the three-dimensional framework provided by the structure in combination with evolutionary trace analysis to pinpoint several surface-exposed regions of potential functional importance and test their importance using mutagenesis. This approach identified a novel functional region important for cell-cell spread. These results suggest a novel role for UL37 in intracellular trafficking that promotes spread of viral infection, which expands the repertoire of UL37 functions in intracellular virus trafficking. Supporting this, the N terminus of UL37 shares a structural similarity with cellular multi-subunit tethering complexes (MTCs), which control vesicular trafficking in eukaryotic cells by tethering transport vesicles to their destination membranes. Our results suggest that UL37 could be the first viral MTC mimic and provide structural rationale for the importance of UL37 for viral trafficking. We propose that herpesviruses may have co-opted MTC functionality of UL37 to bring capsids to cytoplasmic budding destinations and further on to cell junctions for spread to nearby cells. IMPORTANCE: To move within an infected cell, viruses encode proteins that interact with host trafficking machinery. In cells infected with herpesviruses, two capsid-associated proteins control cytosolic movement of capsids by as yet poorly understood mechanisms. Here, we report the crystal structure for the N-terminal half of one of these proteins, UL37. Structure-based mutagenesis revealed a novel function for UL37 in virion trafficking to cell junctions for cell-cell spread. Unexpected structural similarity to components of cellular multi-subunit tethering complexes, which control vesicular traffic, suggests that UL37 could be the first viral MTC mimic and provides structural basis for the importance of UL37 for viral trafficking. Crystal structure of the herpesvirus inner tegument protein UL37 supports its essential role in control of viral trafficking.,Pitts JD, Klabis J, Richards AL, Smith GA, Heldwein EE J Virol. 2014 Mar 5. PMID:24599989[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
