title: Oligomerization of Mumps Virus Phosphoprotein.
abstract: The mumps virus (MuV) genome encodes a phosphoprotein (P) that is important for viral RNA synthesis. P forms the viral RNA-dependent RNA polymerase with the large protein (L). P also interacts with the viral nucleoprotein (NP) and self-associates to form a homotetramer. The P protein consists of three domains, the N-terminal domain (P(N)), the oligomerization domain (P(O)), and the C-terminal domain (P(C)). While P(N) is known to relax the NP-bound RNA genome, the roles of P(O) and P(C) are not clear. In this study, we investigated the roles of P(O) and P(C) in viral RNA synthesis using mutational analysis and a minigenome system. We found that P(N) and P(C) functions can be trans-complemented. However, this complementation requires P(O), indicating that P(O) is essential for P function. Using this trans-complementation system, we found that P forms parallel dimers (P(N) to P(N) and P(C) to P(C)). Furthermore, we found that residues R231, K238, K253, and K260 in P(O) are critical for P's functions. We identified P(C) to be the domain that interacts with L. These results provide structure-function insights into the role of MuV P.
  
  
  OBJECTIVE
  MuV, a paramyxovirus, is an important human pathogen. The P protein of MuV is critical for viral RNA synthesis. In this work, we established a novel minigenome system that allows the domains of P to be complemented in trans. Using this system, we confirmed that MuV P forms parallel dimers. An understanding of viral RNA synthesis will allow the design of better vaccines and the development of antivirals.
authors: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
authors: Adrian
authors: A
authors: Pickar
authors: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
authors: Andrew
authors: A
authors: Elson
authors: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
authors: Yang
authors: Y
authors: Yang
authors: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
authors: Pei
authors: P
authors: Xu
authors: Department of Chemistry, Georgia State University, Atlanta, Georgia, USA.
authors: Ming
authors: M
authors: Luo
authors: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA bhe@uga.edu.
authors: Biao
authors: B
authors: He
mesh_terms: D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008156:Luciferases; D009109:Mumps virus / Q000378:metabolism*; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D058105:Polymerization; D012367:RNA, Viral / Q000096:biosynthesis; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D010750:Phosphoproteins; D012367:RNA, Viral; D014764:Viral Proteins; D008156:Luciferases; C117674:LARGE1 protein, human; D017351:N-Acetylglucosaminyltransferases