Fig. 1: Cryo-EM structures of human LYCHOS.
From: Structural insights into cholesterol sensing by the LYCHOS-mTORC1 pathway
a MST experiments showing that our purified LYCHOS with CHS has a similar binding affinity for GATOR1 (Kd = 7.6 μM) compared with LED (Kd = 12 μM). Values are shown as the mean ± SD from three biologically independent experiments (n = 3). b–d Cryo-EM maps of lipids bound expanded LYCHOSWT_E, CHS bound contracted LYCHOSWT_C and CHS bound contracted LYCHOSY57A_C. The two protomers are colored in slate blue and light coral, and TM15 is shown in deep sky blue. The positions of TM15 of LYCHOSWT_E expanded conformation and LYCHOSY57A_C contracted conformation are indicated by dashed line and solid line. CHS are shown in green, and corresponding cryo-EM map are shown as insets. Other lipid molecules are shown in light gray. e Schematic of the LYCHOS secondary structure features. Regions that are not visible are shown in dashed lines. Densities for α0 are very poor and also shown in dashed cylinders. Residues that affect LYCHOS function in previous studies are shown as red dots. Resolved boundary residues are shown in blue dots. Scaffold domain, transporter domain, GLD, LED, and DEP are shown as gold, purple, deep sky blue, blue and green, respectively. f Structural model of LYCHOSY57A_C shown in cartoon representation. Key domains are colored in protomer A as in (e). TM15 in protomer B is shown in deep sky blue.
