Sandbox Reserved 1765

From Proteopedia

proteopedia linkproteopedia link

==SHOC2-PP1C-MRAS==

spinqualitylabelsall models Caption for this structure Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image This is a default text for your page '. Click above on edit this page' to modify. Be careful with the < and > signs. You may include any references to papers as in: the use of JSmol in Proteopedia [1] or to the article describing Jmol [2] to the rescue. Contents 1 Introduction 2 Relevance 2.1 Cell Proliferation 2.2 Cancer 3 Structure of Subunits 3.1 SHOC2 3.2 PP1C 3.3 MRAS 3.4 Binding of the Subunits 4 Signaling Cascade 4.1 Autoinhibited Confirmation 4.2 Ras/Raf 4.3 Switch I and Switch II 5 Structure of Active Site 5.1 3-Metal Ion Catalysis 5.2 Hydrophobic Binding Site 6 Future Directions Introduction Relevance Cell Proliferation Cancer Structure of Subunits SHOC2 PP1C MRAS Binding of the Subunits Signaling Cascade Autoinhibited Confirmation Ras/Raf Switch I and Switch II Structure of Active Site 3-Metal Ion Catalysis Hydrophobic Binding Site Future Directions This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

Protopedia Resources

<protopedia resources/>

</StructureSection>

References

1. ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
2. ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644

</StructureSection>

Student Contributors

<student contributors/>

SHOC2-PP1C-MRAS is a regulator of a cell proliferation pathway. Mutations in cell proliferation pathways are responsible for 25% of all cancers 1. If this cell proliferation pathway goes unmediated, rapid cell growth and division will occur; the leading cause of cancers is mutations in this pathway. Figure 1 shows the pathway SHOC2-PP1C-MRAS is part of. It is a receptor tyrosine kinase pathway 1. When the receptor binds, a phosphorylation causes a conformational change. This conformation change causes the phosphorylation of other residues. Eventually, this leads to the unbinding of GDP from MRAS and the binding of GTP to MRAS, causing a shift from the open to closed conformation of Switch I. The Switch I 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. When GDP is bound to the MRAS domain, it is in the “open” conformation. Since the gamma phosphate is not bound to GDP, there are no hydrogen bond interactions with the oxygens of the phosphate group- hence the open conformation. Figure 2 When GTP is bound to MRAS, it is in the closed conformation.

  The closed conformation allows for the binding of SHOC2 and PP1C. The open conformation of MRAS sterically clashes with the binding site of SHOC2, which is why the complex is not assembled when GDP is bound, as seen by the highlighted red region.  The only large-scale conformational change occurs in the MRAS subunit. SHOC2 only undergoes a 6° conformational change 1 when MRAS-GTP binds.   Since SHOC2 and PP1C do not undergo much conformational change, they are in an equilibrium of binding and unbinding until MRAS-GTP binds to SHOC2, and the complex is assembled.