Figure 4.

L2 Is a Significant Structural Unit.

(A) Surface representation of the human Ago2 highlighting the large footprint of L2. Note that all domains are interacting with L2.

(B) Structural overview of the missense mutations in L2 with orientation as in (A). The ago1-43 missense mutation is likely to reduce the stability of the interface between the N- and C-lobes.

(C) View of three modeled L2 missense mutations located between the MID (green) and Piwi (gray) domains. The G455R (ago6-6) and L573F (ago1-24) could have an indirect effect on the RNA binding, whereas the destabilization caused by the G579E mutation in ago1-44 is less clear.