The ArgoMid domain is found to be part of the Piwi-lobe of the argonaute proteins. It is composed of a parallel four-stranded beta-sheet core surrounded by four alpha-helices and two additional short alpha-helices. It most closely resembles the amino terminal tryptic core of the E.coli lactose repressor. There is an extensive interface between the Mid and the Piwi domains. The conserved C-terminal half or the Mid has extensive interactions with Piwi, with a deep basic pocket on the surface of the `Mid adjacent to the interface with Piwi. The Mid carries a binding pocket for the 5' phosphate overhang of the guide strand of DNA. The N, Mid, and Piwi domains form a base upon which the PAZ domain sits, resembling a duck. The 5' phosphate and the U1 base are held in place by a conserved network of interactions from protein residues of the Mid and Piwi domains in order to place the guide uniquely in the proper position observed in all Argonaute-RNA complexes.