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It may cause severe disease in immunocompromised people and lead to pregnancy loss or grave disabilities of the fetus upon congenital infection. For effective replication and lifelong persistence in its host, HCMV relies on diverse functions of its tegument protein UL82, also known as pp71. Up to now, little is known about the molecular mechanisms underlying the multiple functions of this crucial viral protein. Here, we describe the X\u2010ray structure of full\u2010length UL82 to a resolution of 2.7\u2009\u00c5. A single polypeptide chain of 559 amino acids mainly folds into three \u00df\u2010barrels. We show that UL82 forms a dimer in the crystal as well as in solution. We identify point mutations that disturb the dimerization interface and show that the mutant protein is monomeric in solution and upon expression in human cells. On the basis of the three\u2010dimensional structure, we identify structural homologs of UL82 from other herpesviruses and analyze whether their functions are preserved in UL82. We demonstrate that UL82, despite its structural homology to viral deoxyuridinetriphosphatases (dUTPases), does not possess dUTPase activity. Prompted by the structural homology of UL82 to the ORF10 protein of murine herpesvirus 68 (MHV68), which is known to interact with the RNA export factor ribonucleic acid export 1 (Rae1), we performed coimmunoprecipitations and demonstrated that UL82 indeed interacts with Rae1. This suggests that HCMV UL82 may play a role in mRNA export from the nucleus similar to ORF10 encoded by the gammaherpesviruses MHV68.<\/jats:p>","DOI":"10.1002\/pro.4915","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T13:45:06Z","timestamp":1708004706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Crystal structure of the tegument protein <scp>UL82<\/scp> (pp71) from human cytomegalovirus"],"prefix":"10.1002","volume":"33","author":[{"given":"Jan","family":"Eberhage","sequence":"first","affiliation":[{"name":"Institute for Biophysical Chemistry Hannover Medical School  Hannover Germany"},{"name":"Cluster of Excellence RESIST (EXC 2155) Hannover Medical School  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian P.","family":"Bresch","sequence":"additional","affiliation":[{"name":"Institute for Biophysical Chemistry Hannover Medical 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