Fig. 7

Mapping cancer-associated mutations in the homology model of the DLC1-START domain and structural analysis suggesting the putative binding site of lipid (PS) and interacting proteins. A Cartoon representation of the homology model of the DLC1-START domain, generated using the DLC2-START domain as a template. N- and C-terminal ends are indicated. B Cancer-associated mutations mapped on the DLC1-START domain that has normal (green) and impaired (red) binding to Caveolin-1 and PLCD1. C Analysis of cavity and tunnels in the model of the DLC1-START domain shows the potential binding site of the lipid (PS). The empty space that forms this tunnel is shown in yellow. D Cancer-associated mutations mapped on the DLC1-START domain that show normal (green) and impaired (red) binding to PS. E Model of the DLC1-START domain with residues from 929 to 957 highlighted in blue. The deletion of this region has been shown to abolish the DLC1-Caveolin-1 interaction. F Model showing orientation and positioning of the DLC1-START domain at the membrane. The computational approach was used to identify residues involved in the initial docking of the DLC1-START domain with the membrane interface. The lipid headgroups of the membrane bilayer that point towards the cytoplasm are shown as blue colored spheres. G Western blot in cytosolic, membrane and total cell lysates from H1299 cells transfected with GFP or the C2 domain of Lactadherin, using the indicated antibodies