Sandbox Reserved 1767: Difference between revisions
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=== Switch I and Switch II === | === Switch I and Switch II === | ||
[[Image:RASRAF.png| | [[Image:RASRAF.png|400 px|right|thumb|Figure 2: MRAS SWI and SWII open and closed conformations.<ref name="Liau">PMID: 35768504</ref>.]] | ||
SHOC2-PP1C-MRAS is a central gatekeeper in receptor tyrosine kinase signaling 1. Figure 1 shows the specific pathways SHOC2-PP1C-MRAS mediates. When MRAS is bound to GDP, shown in the left of figure 1, Raf is bound to a 14-3-3 protein dimer restricting it to the cytoplasm. When MRAS-GDP is exchanged for GTP via a nucleotide exchange factor GEF, a conformational change occurs. This change figure 2, causes a shift from the open to closed conformation of Switch I. figure 3 Green link The Switch I (SWI) region is made up of residues 42-48 of the MRAS domain. 1 These residues are crucial for the binding of MRAS, SHOC2, and PP1C because MRAS undergoes a conformational change that allows for SMP complex assembly upon GTP binding. Figure 2 When GTP is bound to MRAS, it is in the “closed conformation” because hydrogen bond interactions between the γ phosphate of GTP and residues in the SWI region of MRAS cause SWI to adopt a closed conformation. The closed conformation allows for the binding of SHOC2 and PP1C because there is no steric clash GREEN LINK between the SWI region of MRAS and the surface of SHOC2 when GTP is bound. Green link. The only large-scale conformational change occurs in the MRAS subunit. When GDP is bound to the MRAS domain, it is in the “open” conformation. Green link Since the γ-phosphate is not bound to GDP, there are no hydrogen bond interactions with the oxygens of the γ-phosphate group and the MRAS SWI region, causing MRAS to adpot an "open" conformation. Since SHOC2 and PP1C do not undergo much conformational change, they are in a slow equilibrium of binding and unbinding until MRAS binds to GTP allowing MRAS to bind to SHOC2 and PP1C. | SHOC2-PP1C-MRAS is a central gatekeeper in receptor tyrosine kinase signaling 1. Figure 1 shows the specific pathways SHOC2-PP1C-MRAS mediates. When MRAS is bound to GDP, shown in the left of figure 1, Raf is bound to a 14-3-3 protein dimer restricting it to the cytoplasm. When MRAS-GDP is exchanged for GTP via a nucleotide exchange factor GEF, a conformational change occurs. This change figure 2, causes a shift from the open to closed conformation of Switch I. figure 3 Green link The Switch I (SWI) region is made up of residues 42-48 of the MRAS domain. 1 These residues are crucial for the binding of MRAS, SHOC2, and PP1C because MRAS undergoes a conformational change that allows for SMP complex assembly upon GTP binding. Figure 2 When GTP is bound to MRAS, it is in the “closed conformation” because hydrogen bond interactions between the γ phosphate of GTP and residues in the SWI region of MRAS cause SWI to adopt a closed conformation. The closed conformation allows for the binding of SHOC2 and PP1C because there is no steric clash GREEN LINK between the SWI region of MRAS and the surface of SHOC2 when GTP is bound. Green link. The only large-scale conformational change occurs in the MRAS subunit. When GDP is bound to the MRAS domain, it is in the “open” conformation. Green link Since the γ-phosphate is not bound to GDP, there are no hydrogen bond interactions with the oxygens of the γ-phosphate group and the MRAS SWI region, causing MRAS to adpot an "open" conformation. Since SHOC2 and PP1C do not undergo much conformational change, they are in a slow equilibrium of binding and unbinding until MRAS binds to GTP allowing MRAS to bind to SHOC2 and PP1C. | ||
