Sandbox Reserved 1777
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==SHOC2== | ==SHOC2== | ||
[[Image:SHOC2-PP1C-MRAS Surface.JPG|300px|right|thumb|<font size="2"><div style="text-align: center;">'''Figure 2'''. Surface representation of SHOC2-PP1C-MRAS ([https://www.rcsb.org/structure/7UPI PDB 7upi]). SHOC2 (blue), PP1C (orange) and MRAS (green). </div></font>]] | [[Image:SHOC2-PP1C-MRAS Surface.JPG|300px|right|thumb|<font size="2"><div style="text-align: center;">'''Figure 2'''. Surface representation of SHOC2-PP1C-MRAS ([https://www.rcsb.org/structure/7UPI PDB 7upi]). SHOC2 (blue), PP1C (orange) and MRAS (green). </div></font>]] | ||
- | SHOC2 is a scaffolding protein which acts as a cradle to bind PP1C and MRAS | + | SHOC2 is a scaffolding protein which acts as a cradle to bind PP1C and MRAS <ref name="Hauseman" />, serving as an aggregation point to enable reciprocal interactions between these 3 signaling proteins. <scene name='95/952705/Shoc2_structure/1'>SHOC2</scene> is a leucine rich repeat ([https://en.wikipedia.org/wiki/Leucine-rich_repeat LRR]) protein consisting of 20 consecutive <scene name='95/952706/Shoc2_structure/6'>LRR motifs</scene>. LRR motifs form an an extended β-sheet on the inner concave surface of SHOC2 with α-helices facing outward, '''which help bind the whole protein'''. These LRR motifs result in a largely hydrophobic core '''within the concaved region'''.<Ref name= 'Hahn'> Kwon, J. J., & Hahn, W. C. A Leucine-Rich Repeat Protein Provides a SHOC2 the RAS Circuit: a Structure-Function Perspective. Molecular and cellular biology, 41(4), e00627-20 (2021). doi:10.1128/MCB.00627-20. [http://doi.org/10.1128/MCB.00627-20. DOI: 10.1128/MCB.00627-20]. </Ref>. |
==PP1C== | ==PP1C== |
Revision as of 15:43, 11 April 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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References
- ↑ 1.0 1.1 Bernal Astrain G, Nikolova M, Smith MJ. Functional diversity in the RAS subfamily of small GTPases. Biochem Soc Trans. 2022 Apr 29;50(2):921-933. doi: 10.1042/BST20211166. DOI:10.1042/BST20211166
- ↑ Molina JR, Adjei AA. The Ras/Raf/MAPK pathway. J Thorac Oncol. 2006 Jan;1(1):7-9. DOI:10.1016/S1556-0864(15)31506-9.
- ↑ Li, L., Zhao, G. D., Shi, Z. et. al.The Ras/Raf/MEK/ERK signaling pathway (Figure 1) and its role in the occurrence and development of HCC. Oncology letters, 12(5), 3045–3050. DOI:10.3892/ol.2016.5110.
- ↑ 4.0 4.1 4.2 Hauseman, Z.J., Fodor, M., Dhembi, A. et al. Structure of the MRAS–SHOC2–PP1C phosphatase complex. Nature 609, 416–423 (2022). doi: 10.1038/s41586-022-05086-1. DOI:10.1038/s41586-022-05086-1.
- ↑ Kwon, J. J., & Hahn, W. C. A Leucine-Rich Repeat Protein Provides a SHOC2 the RAS Circuit: a Structure-Function Perspective. Molecular and cellular biology, 41(4), e00627-20 (2021). doi:10.1128/MCB.00627-20. DOI: 10.1128/MCB.00627-20.
- ↑ Young, L., Rodriguez-Viciana, P. MRAS: A Close but Understudied Member of the RAS Family. Cold Spring Harbor Perspectives in Medicine (2018). doi: 10.1101/cshperspect.a033621. DOI: 0.1101/cshperspect.a033621.
- ↑ 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.
- ↑ 8.0 8.1 8.2 8.3 8.4 Kwon, J.J., Hajian, B., Bian, Y. et al. Structure–function analysis of the SHOC2–MRAS–PP1C holophosphatase complex. Nature 609, 408–415 (2022).doi: 10.1038/s41586-022-04928-2. DOI:10.1038/s41586-022-04928-2
- ↑ 9.0 9.1 9.2 Kwon, J., Jajian, B., Bian, Y. et al. Comprehensive structure-function evaluation of the SHOC2 holophosphatase reveals disease mechanisms and therapeutic opportunities. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022. DOI: 10.1158/1538-7445.AM2022-LB029.
- ↑ 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
- ↑ 11.0 11.1 Lavoie, H., Therrien, M. Structural keys unlock RAS–MAPK cellular signalling pathway. Nature 609, 248-249 (2022). doi: 10.1038/d41586-022-02189-7. DOI:10.1038/d41586-022-02189-7.
- ↑ 12.0 12.1 van der Burgt, I. Noonan syndrome. Orphanet J Rare Dis 2, 4 (2007). doi: 10.1186/1750-1172-2-4 DOI: 10.1186/1750-1172-2-4.