The Tat protein of the caprine arthritis encephalitis virus interacts with the Notch2 EGF-like repeats and the epithelin/granulin precursor.
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.
Shoham
Nitza
N
Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Cohen
Limor
L
Gazit
Arnona
A
Yaniv
Abraham
A
D000818:Animals; D016088:Arthritis-Encephalitis Virus, Caprine / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D015696:Gene Products, tat / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006041:Goats; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000077153:Progranulins; D017434:Protein Structure, Tertiary; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D020798:Two-Hybrid System Techniques
D004279:DNA, Viral; D015696:Gene Products, tat; D036341:Intercellular Signaling Peptides and Proteins; C497764:NOTCH2 protein, human; D000077153:Progranulins; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface