FIGURE 8.

Model of Rep68 assembly on AAVS1 site. A, model of Rep68 bound to a 50-mer DNA. The model was based on the structure of the AAV5-OBD/RBS complex (Protein Data Bank code 1RZ9). The linker was modeled as an extended region to allowed interaction with DNA. Four Rep68 molecules are colored green (Rep68–1), light green (Rep68–2), blue (Rep68–3), and red (Rep68–4). Individual domains are labeled accordingly. The helicase domain (HD₄) of Rep68–4 clashes with both the OBD₁ and HD₁ of the Rep68–1 molecule. B, oligomer of Rep68 (shown as a dimer) binds DNA using the helicase and OBD domains. Upon encountering the RBS site through specific contacts with the OBD domain, additional molecules are recruited, and the heptameric complex is assembled. Helicase domain is represented in blue, and OBD domain is green. Three direct repeats in the AAVS1 site are red, orange, and pink.