U24 from Roseolovirus Interacts Strongly with Nedd4 WW Domains
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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.
Yuan Y, Fang A, Wang Z, Chen H, Fu Z, Zhou M Autophagy. 2024; 20(8):1723-1740.
PMID: 38566321 PMC: 11262214. DOI: 10.1080/15548627.2024.2338575.
Sokolovska L, cistjakovs M, Matroze A, Murovska M, Sultanova A Microorganisms. 2024; 12(2).
PMID: 38399766 PMC: 10892088. DOI: 10.3390/microorganisms12020362.
Studying the Interactions of U24 from HHV-6 in Order to Further Elucidate Its Potential Role in MS.
Pi K, Bortolotti D, Sang Y, Schiuma G, Beltrami S, Rizzo S Viruses. 2022; 14(11).
PMID: 36366483 PMC: 9696605. DOI: 10.3390/v14112384.
Viral Proteins with PxxP and PY Motifs May Play a Role in Multiple Sclerosis.
Pi K, Sang Y, Straus S Viruses. 2022; 14(2).
PMID: 35215874 PMC: 8879583. DOI: 10.3390/v14020281.
Athanasiou E, Gargalionis A, Boufidou F, Tsakris A Int J Mol Sci. 2021; 22(5).
PMID: 33668202 PMC: 7956256. DOI: 10.3390/ijms22052250.