Sandbox Reserved 1767
From Proteopedia
(Difference between revisions)
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== Introduction == | == Introduction == | ||
+ | SHOC2-MRAS-PP1C, also known as the SMP complex, is a 3-subunit complex essential for cell proliferation and the survival of many cancers and RASopathies. When the subunits comes together, it plays a key role in the activation of the Ras-Raf complex and signaling cascade. Each subunit of the complex has an individual structure which correlates with its function. SHOC2 has a crescent shape in order to enhance substrate interactions and interactions between the subunits while PP1C holds the catalytic active site and the C-terminus MRAS localizes the complex to the cell membrane. Mutations in one or multiple of these subunits leads to over-activation of the signaling pathway, leading to cancer and developmental disorders called RASopathies. The signaling cascade is kept from over-activating by being held in an auto-inhibited conformation. The SMP complex is responsible for removing this auto-inhibited conformation, allowing for Raf to bind to Ras. Mutations in the subunits can lead to more frequent complex formation, ultimately leading to more cell proliferation. SHOC2-PP1C-MRAS is being studied as a possible treatment target for many types of cancers. | ||
== Relevance == | == Relevance == | ||
=== Cell Proliferation === | === Cell Proliferation === | ||
- | + | The Ras-Raf signaling cascade as a whole is fundamental for cell proliferation. It regulates cell growth and survival, and the SHOC2-PP1C-MRAS complex removes the inhibitory phosphate on RAF, allowing for signaling to initiate. | |
- | == Structure of Subunits == | + | === Cancer and RASopathies === |
+ | - mutations are at the protein-protein interaction surfaces, leads to more stability of the complex and increased interaction energy of SHOC2 with PP1c and/or MRAS. | ||
+ | - other RAS proteins can bind in a mutated complex rather than just MRAS | ||
+ | - SHOC2 is necessary in all cases | ||
+ | == Structure of Subunits == | ||
=== SHOC2 === | === SHOC2 === | ||
=== PP1C === | === PP1C === | ||
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PP1C has a <scene name='95/952695/Hydrophobic_bindning_site/3'>hydrophobic binding site</scene> adjacent to its active site. The majority of PP1C targets are able to bind through a specific motif that is recognized by the hydrophobic groove. In the Ras/Raf signaling cascade, the region of Raf that is C-terminal to the phosphate group binds to the hydrophobic groove, and the remaining residues bind to the hydrophobic region of SHOC2. This binding to SHOC2 is what allows the SMP complex to be more specific than PP1C on its own. | PP1C has a <scene name='95/952695/Hydrophobic_bindning_site/3'>hydrophobic binding site</scene> adjacent to its active site. The majority of PP1C targets are able to bind through a specific motif that is recognized by the hydrophobic groove. In the Ras/Raf signaling cascade, the region of Raf that is C-terminal to the phosphate group binds to the hydrophobic groove, and the remaining residues bind to the hydrophobic region of SHOC2. This binding to SHOC2 is what allows the SMP complex to be more specific than PP1C on its own. | ||
== Future Directions == | == Future Directions == | ||
- | + | - knockdown of SHOC2 | |
Revision as of 18:02, 30 March 2023
This Sandbox is Reserved from February 27 through August 31, 2023 for use in the course CH462 Biochemistry II taught by R. Jeremy Johnson at the Butler University, Indianapolis, USA. This reservation includes Sandbox Reserved 1765 through Sandbox Reserved 1795. |
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Contents |
SHOC2-PP1C-MRAS
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Protopedia Resources
<protopedia resources/>
</StructureSection>
References
- ↑ 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
- ↑ 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/>