title: U24 from Roseolovirus interacts strongly with Nedd4 WW Domains.
abstract: U24 is a protein found in both roseoloviruses Human Herpes Virus type 6 and 7 (HHV-6 and HHV-7), with an N-terminus that is rich in prolines (PY motif in both HHV-6A and 7; PxxP motif in HHV-6A). Previous work has shown that the interaction between U24 and WW domains is important for endocytic recycling of T-cell receptors, but a cognate ligand was never identified. In this contribution, data was obtained from pull-downs, ITC, NMR and molecular dynamics simulations to show that a specific interaction exists between U24 and Nedd4 WW domains. ITC experiments were also carried out for U24 from HHV-6A phosphorylated at Thr6 (pU24-6A) and a peptide containing the PY motif from Nogo-A, a protein implicated in both the initial inflammatory and the neurodegenerative phases of multiple sclerosis (MS). The results suggest that phosphorylation of U24 from HHV-6A may be crucial for its potential role in MS.
authors.affiliation: Department of Chemistry, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Yurou
authors.initials: Y
authors.lastname: Sang
authors.affiliation: Department of Chemistry, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Walter R P
authors.initials: WR
authors.lastname: Scott
authors.affiliation: Michael Smith Laboratories and Department of Chemical and Biological Engineering, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: A Louise
authors.initials: AL
authors.lastname: Creagh
authors.affiliation: Michael Smith Laboratories and Department of Chemical and Biological Engineering, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Haynes
authors.affiliation: Department of Chemistry, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Suzana K
authors.initials: SK
authors.lastname: Straus
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D004705:Endocytosis; D015654:Herpesvirus 6, Human / Q000502:physiology*; D006801:Humans; D056004:Molecular Dynamics Simulation; D018716:Molecular Mimicry; D009103:Multiple Sclerosis / Q000378:metabolism / Q000821:virology*; D000070798:Nogo Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011392:Proline / Q000235:genetics; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D000074585:WW Domains / Q000235:genetics
chemical_list: D000070798:Nogo Proteins; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins; D011392:Proline