Overall scheme of Get3 chaperone pathway. Get3 dimer (I) after binding to ATP (II) can interact with the Get4/5 heterotetrameric complex stabilized by Ge4/4 and Get5/5 binding interfaces (III). The ATP binding increases the affinity of Get3 dimer to Get4, and Get3 can disrupt the Get4/4 binding interface and create the hexameric complex with Get4/5 via two Get3/4 interaction interfaces (IV). Sgt2 dimer with TA protein cargo binds to Get3/4/5complex via Sgt2/Get5 interface. After the binding, the cargo is transferred to Get3 dimer (V). The binding of the cargo to Get3 triggers dissociation of the complex to Sgt2 dimer, Get4/5 heterotetramer, and Get3 dimer bound to TA protein (VI). In the next steps, the Get3 with the cargo is transferred to the ER. To see this figure in color, go online.