Figure 2.

The overall structure of the Merlin-FERM/Merlin-CTD complex. (A) Ribbon diagram showing the crystal structure of the stabilized, fully closed Merlin-FERM/Merlin-CTD complex. S518D is shown in the stick model and colored in red. (B) Comparison of the structures of the Merlin FERM/CTD complex and the Moesin FERM/CTD complex (PDB code: 1EF1). In this representation, the Merlin-CTD and Moesin-CTD are shown as ribbons, and the Merlin-FERM is drawn in the surface model based on the degree of their amino acid sequence conservation between Merlin and ERMs. The N-terminal half of Merlin α1_CTD is boxed in red to emphasize its structural uniqueness. (C) Sequence alignment of the CTD regions from Merlin across different species and human Moesin-CTD. Secondary structural elements for Merlin-CTD and Moesin-CTD are indicated above and below the alignment, respectively. Residues involved in the auto-inhibition of Merlin are emphasized in orange and S518 is highlighted in red and with an asterisk. The residues within the red box form the first half of α1_CTD highlighted in red box in B. (D) Molecular details of the Merlin FERM/CTD interaction. (E, F) Ribbon-dot model (E) and a schematic diagram (F) summarizing 21 human cancer-related missense mutations. The mutations that are predicted to interfere with the folding of FERM are shown in red; the mutations that may alter the auto-inhibition and/or AMOT binding of Merlin are colored in cyan and blue.