1. The Tat protein of the caprine arthritis encephalitis virus interacts with the Notch2 EGF-like repeats and the epithelin/granulin precursor
- Author
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N.G. Shoham, Arnona Gazit, Abraham Yaniv, and Limor Cohen
- Subjects
Repetitive Sequences, Amino Acid ,Proepithelin ,Arthritis-Encephalitis Virus, Caprine ,Receptors, Cell Surface ,In Vitro Techniques ,Hiv 1 tat ,Cell Line ,Progranulins ,Virology ,Two-Hybrid System Techniques ,Animals ,Humans ,Receptor, Notch2 ,Caprine arthritis encephalitis virus ,Binding Sites ,biology ,Base Sequence ,cDNA library ,Goats ,virus diseases ,Human placenta ,biology.organism_classification ,Molecular biology ,Yeast ,Protein Structure, Tertiary ,Infectious Diseases ,Lentivirus ,DNA, Viral ,Gene Products, tat ,Intercellular Signaling Peptides and Proteins - Abstract
Using the yeast two-hybrid system, we screened a human placenta cDNA library and identified two proteins that interacted with the Tat protein of the caprine arthritis encephalitis virus (CAEV): the EGF-like repeats 1–6 of the extracellular domain of the human Notch2 receptor and the epithelin/granulin growth factor precursor. This interaction was also confirmed in mammalian cells. Using in vitro mutagenesis assays, we showed that each one of the three cysteine residues located within the cysteine-rich domain of the CAEV Tat protein is essential for the binding of Tat to both the Notch2 and the epithelin/granulin protein. It is thus suggested that the cysteine-rich domain of Tat plays a role in the interaction between the Tat and either Notch2 or the epithelin/granulin domains, both of which exhibit EGF-like-repeat-imposed spatial conformation. It is assumed that such interactions might modulate the physiological functions of Notch2 and epithelin/granulin, thereby affecting various pathologies associated with CAEV.
- Published
- 2003