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Sandbox Reserved 1777

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Revision as of 19:30, 26 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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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.

1 Switch I and II
2 Binding Pocket
3 Relevance
4 Structural highlights

Switch I and II

Switch I and II are located on MRAS. The switches determine whether MRAS can bind to SHOC2-PP1C. The switches have to go through a conformational change to allow binding of SHOC2-PP1C to MRAS. This conformational change is caused by GTP replacing GDP. Once GTP is added MRAS shifts and binds with SHOC2. When GDP is bound to MRAS switch II is moved outward which causes a steric clash with SHOC2 . When GTP is bound, switch II can form various hydrophobic interactions with SHOC2^[3]. . Interactions are strengthened with hydrogen bonding and pi stacking. When MRAS is bound to SHOC2-PP1C, switch I has an important role in making interactions with PP1C.

Binding Pocket

Once all the domains are bound NTpS binds to PP1C in the active site. Once the NTpS is bound it becomes dephosphorylated and the complex falls apart. NTpS is dephosphorylated to prevent the active dimeric RAF from inactivating and changing into its monomeric structure. The NTpS active site is surrounded by hydrophobic and acidic regions along with C-terminal. (). These regions are located on the surface of PP1C whereas the active site is placed further into the structure. It is thought that these regions help the ligand bind to the active site by making interactions that will lead NTpS into the protein. There is still some uncertainty as to how the substrate selectivity works but these regions could play an essential role in it. Specifically, the C-terminal of the pS from NTpS would bind to the hydrophobic region on PP1C^[4].

NTpS can bind to the PP1C active site without PP1C also being bound to SHOC2 and MRAS, however the catalytic activity is much slower and the reaction is less efficient. Also for this event to occur NTpS would need to be exposed from its binding site in the inactive RAF complex. A RAS has to bind to RAF to expose the NTpS allowing PP1C and NTpS to bind.

Relevance

Structural highlights

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.

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
↑ Daniel A. Bonsor, Patrick Alexander, Kelly Snead, Nicole Hartig, Matthew Drew, Simon Messing, Lorenzo I. Finci, Dwight V. Nissley, Frank McCormick, Dominic Esposito, Pablo Rodrigiguez-Viciana, Andrew G. Stephen, Dhirendra K. Simanshu. Structure of the SHOC2–MRAS–PP1C complex provides insights into RAF activation and Noonan syndrome. bioRxiv. 2022.05.10.491335. doi: 10.1101/2022.05.10.491335. DOI:10.1101/2022.05.10.491335.
↑ Liau NPD, Johnson MC, Izadi S, Gerosa L, Hammel M, Bruning JM, Wendorff TJ, Phung W, Hymowitz SG, Sudhamsu J. Structural basis for SHOC2 modulation of RAS signalling. Nature. 2022 Jun 29. pii: 10.1038/s41586-022-04838-3. doi:, 10.1038/s41586-022-04838-3. PMID:35768504 doi:http://dx.doi.org/10.1038/s41586-022-04838-3

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Sandbox Reserved 1777

From Proteopedia

Revision as of 19:30, 26 March 2023

Your Heading Here (maybe something like 'Structure')

Contents

Switch I and II

Binding Pocket

Relevance

Structural highlights

References

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