Sandbox Reserved 1776: Difference between revisions

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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 <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.~~

== Introduction ==

~~The active holoenzyme contains 3 domains. The SHOC-2(blue), PP1C(coral), and MRAS (green) domains form the complete <scene name='95/952704/Smpcolored/1'>SMP complex. </scene>~~

SHOC-2 is a scaffolding protein <scene name='95/952704/Shoc2_cradle/1'>scaffolding protein</scene> that holds the other subunits in the correct orientation, allowing for the holoenzyme to be functional.

=== Biological Introduction ===

SHOC2-PP1C-MRAS is a human enzyme that is involved in regulating cell proliferation and division<Ref name='Astrain'>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. [https://doi.org/10.1042/BST20211166. DOI:10.1042/BST20211166]. </Ref>. The enzyme is involved in the vast RAS-MAPK pathway, which is initially activated by an extracellular growth factor binding to a membrane bound RAS GTPase[https://www.mechanobio.info/what-is-mechanosignaling/what-are-small-gtpases/what-are-ras-gtpases/] such as HRAS, NRAS, or KRAS. RAS-GTPases are a family of proteins that work by functioning as molecular switches[https://www.frontiersin.org/articles/10.3389/fonc.2019.01088/full#:~:text=In%20human%20cells%2C%20three%20closely,proliferation%20and%20survival%20among%20others]. This occurs from the protein alternating between binding GTP to be active and GDP to be inactive <ref name="Astrain" />. After activation via an extracellular growth factor, the RAS-GTPase enzyme binds GTP, which activates RAF<Ref name='Molina'>Molina JR, Adjei AA. The Ras/Raf/MAPK pathway. J Thorac Oncol. 2006 Jan;1(1):7-9. [https://doi.org/10.1016/S1556-0864(15)31506-9. DOI:10.1016/S1556-0864(15)31506-9]. </Ref>.

=== Structural Introduction ===

The enzyme requires 3 domains (SHOC-2(blue), PP1C(coral), and MRAS (green)) to form the active enzyme (SMP Complex), also known as a <scene name='95/952704/Smpcolored/1'>holoenzyme </scene> <Ref name='Hauseman'>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. [https://doi.org/10.1038/s41586-022-05086-1. DOI:10.1038/s41586-022-05086-1]. </Ref>. SHOC-2 is a scaffolding protein <scene name='95/952704/Shoc2_cradle/1'>scaffolding protein</scene> that holds the other subunits in the correct orientation, allowing for the holoenzyme to be functional. PP1C is a catalytic domain of a phosphatase enzyme PP1[https://proteopedia.org/wiki/index.php/Protein_phosphatase], which cleaves ____. MRAS is a GTPase protein and is located near (typically just below) the cell membrane. When MRAS binds GTP, it becomes active and triggers the assembly of the active holoenzyme<ref name="Hauseman" />. The SMP complex was determined via cryo-electron microscopy as well as x-ray diffraction. These studies found that PP1C and MRAS occupy the concave surface of SHOC2, leaving the catalytic site of PP1C and the substrate binding cleft in MRAS exposed.

== Sources ==

Liau <Ref name='Liau'>Liau, N.P.D., Johnson, M.C., Izadi, S. et al. Structural basis for SHOC2 modulation of RAS signalling. Nature 609, 400–407 (2022).doi: 10.1038/s41586-022-04838-3. [https://doi.org/10.1038/s41586-022-04838-3. DOI:10.1038/s41586-022-04838-3]. </Ref>

Hauseman<ref name="Hauseman" />

Kwon <Ref name='Kwon'>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. [https://doi.org/10.1038/s41586-022-04928-2. DOI:10.1038/s41586-022-04928-2]. </Ref>

Lavoie <Ref name='Lavoie'>Lavoie, H., Therrien, M. Structural keys unlock RAS–MAPK cellular signalling pathway. Nature 609, 248-249 (2022). doi: 10.1038/d41586-022-02189-7. [https://doi.org/10.1038/d41586-022-02189-7. DOI:10.1038/d41586-022-02189-7]. </Ref>

Abstract LB029<Ref name= 'Jajian'>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. [https://aacrjournals.org/cancerres/article/82/12_Supplement/LB029/699443. DOI: 10.1158/1538-7445.AM2022-LB029]. </Ref>

Bonsor<Ref name= 'Bonsor'>Bonsor, D., Alexander, P., Snead, K. et al. Structure of the SHOC2–MRAS–PP1C complex provides insights into RAF activation and Noonan syndrome. Nat Struct Mol Biol 29, 966–977 (2022). doi:10.1038/s41594-022-00841-4. [https://doi.org/10.1038/s41594-022-00841-4. DOI: 10.1038/s41594-022-00841-4]. </Ref>

Young(MRAS section) <Ref name= 'Young'>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. [https://perspectivesinmedicine.cshlp.org/content/8/12/a033621.full.pdf+html. DOI: 0.1101/cshperspect.a033621]. </Ref>

Kwon and Hahn (SHOC2 section) <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 section [https://www.ncbi.nlm.nih.gov/gene/5499 external link]

blue link LRR [https://en.wikipedia.org/wiki/Leucine-rich_repeat LRR]

Arkun (for ERK signaling) <Ref name= 'Arkun'> Arkun, Y., & Yasemi, M. Dynamics and control of the ERK signaling pathway: Sensitivity, bistability, and oscillations. PloS one, 13(4), e0195513. doi: 10.1371/journal.pone.0195513 [https://doi.org/10.1371/journal.pone.0195513. DOI: 10.1371/journal.pone.0195513]. </Ref>

For last sentence in implications van der Burgt <Ref name= 'van der Burgt'> van der Burgt, I. Noonan syndrome. Orphanet J Rare Dis 2, 4 (2007). doi: 10.1186/1750-1172-2-4 [https://doi.org/10.1186/1750-1172-2-4. DOI: 10.1186/1750-1172-2-4]. </Ref>

PP1C REF: <Ref name= 'Aggen'> Aggen, J., Nairn, A., Chamberlin, R. Regulation of protein phosphatase-1. Chemistry & Biology 2000, 7:R13–R23. [https://www.cell.com/cell-chemical-biology/pdf/S1074-5521(00)00069-7.pdf]. </Ref>.

~~== Biological Function ==~~

== Relevance ==

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This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>

== References ==

Sandbox Reserved 1776: Difference between revisions

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@@ Line 3: / Line 3: @@
 <StructureSection load='7UPI' size='350' frame='true' side='right' caption='SHOC2-PP1C-MRAS holoenzyme complex' scene=''>
 This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.
-You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.
 == Introduction ==
-The active holoenzyme contains 3 domains. The SHOC-2(blue), PP1C(coral), and MRAS (green) domains form the complete <scene name='95/952704/Smpcolored/1'>SMP complex. </scene>
-SHOC-2 is a scaffolding protein <scene name='95/952704/Shoc2_cradle/1'>scaffolding protein</scene> that holds the other subunits in the correct orientation, allowing for the holoenzyme to be functional.
+=== Biological Introduction ===
+SHOC2-PP1C-MRAS is a human enzyme that is involved in regulating cell proliferation and division<Ref name='Astrain'>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. [https://doi.org/10.1042/BST20211166. DOI:10.1042/BST20211166]. </Ref>. The enzyme is involved in the vast RAS-MAPK pathway, which is initially activated by an extracellular growth factor binding to a membrane bound RAS GTPase[https://www.mechanobio.info/what-is-mechanosignaling/what-are-small-gtpases/what-are-ras-gtpases/] such as HRAS, NRAS, or KRAS. RAS-GTPases are a family of proteins that work by functioning as molecular switches[https://www.frontiersin.org/articles/10.3389/fonc.2019.01088/full#:~:text=In%20human%20cells%2C%20three%20closely,proliferation%20and%20survival%20among%20others]. This occurs from the protein alternating between binding GTP to be active and GDP to be inactive <ref name="Astrain" />. After activation via an extracellular growth factor, the RAS-GTPase enzyme binds GTP, which activates RAF<Ref name='Molina'>Molina JR, Adjei AA. The Ras/Raf/MAPK pathway. J Thorac Oncol. 2006 Jan;1(1):7-9. [https://doi.org/10.1016/S1556-0864(15)31506-9. DOI:10.1016/S1556-0864(15)31506-9]. </Ref>.
+=== Structural Introduction ===
+The enzyme requires 3 domains (SHOC-2(blue), PP1C(coral), and MRAS (green)) to form the active enzyme (SMP Complex), also known as a <scene name='95/952704/Smpcolored/1'>holoenzyme </scene> <Ref name='Hauseman'>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. [https://doi.org/10.1038/s41586-022-05086-1. DOI:10.1038/s41586-022-05086-1]. </Ref>. SHOC-2 is a scaffolding protein <scene name='95/952704/Shoc2_cradle/1'>scaffolding protein</scene> that holds the other subunits in the correct orientation, allowing for the holoenzyme to be functional. PP1C is a catalytic domain of a phosphatase enzyme PP1[https://proteopedia.org/wiki/index.php/Protein_phosphatase], which cleaves ____. MRAS is a GTPase protein and is located near (typically just below) the cell membrane. When MRAS binds GTP, it becomes active and triggers the assembly of the active holoenzyme<ref name="Hauseman" />. The SMP complex was determined via cryo-electron microscopy as well as x-ray diffraction. These studies found that PP1C and MRAS occupy the concave surface of SHOC2, leaving the catalytic site of PP1C and the substrate binding cleft in MRAS exposed.
+== Sources ==
+Liau <Ref name='Liau'>Liau, N.P.D., Johnson, M.C., Izadi, S. et al. Structural basis for SHOC2 modulation of RAS signalling. Nature 609, 400–407 (2022).doi: 10.1038/s41586-022-04838-3. [https://doi.org/10.1038/s41586-022-04838-3. DOI:10.1038/s41586-022-04838-3]. </Ref>
+Hauseman<ref name="Hauseman" />
+Kwon <Ref name='Kwon'>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. [https://doi.org/10.1038/s41586-022-04928-2. DOI:10.1038/s41586-022-04928-2]. </Ref>
+Lavoie <Ref name='Lavoie'>Lavoie, H., Therrien, M. Structural keys unlock RAS–MAPK cellular signalling pathway. Nature 609, 248-249 (2022). doi: 10.1038/d41586-022-02189-7. [https://doi.org/10.1038/d41586-022-02189-7. DOI:10.1038/d41586-022-02189-7]. </Ref>
+Abstract LB029<Ref name= 'Jajian'>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. [https://aacrjournals.org/cancerres/article/82/12_Supplement/LB029/699443. DOI: 10.1158/1538-7445.AM2022-LB029]. </Ref>
+Bonsor<Ref name= 'Bonsor'>Bonsor, D., Alexander, P., Snead, K. et al. Structure of the SHOC2–MRAS–PP1C complex provides insights into RAF activation and Noonan syndrome.  Nat Struct Mol Biol 29, 966–977 (2022). doi:10.1038/s41594-022-00841-4. [https://doi.org/10.1038/s41594-022-00841-4. DOI: 10.1038/s41594-022-00841-4]. </Ref>
+Young(MRAS section) <Ref name= 'Young'>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. [https://perspectivesinmedicine.cshlp.org/content/8/12/a033621.full.pdf+html. DOI: 0.1101/cshperspect.a033621]. </Ref>
+Kwon and Hahn (SHOC2 section) <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 section [https://www.ncbi.nlm.nih.gov/gene/5499 external link]
+blue link LRR [https://en.wikipedia.org/wiki/Leucine-rich_repeat LRR]
+Arkun (for ERK signaling) <Ref name= 'Arkun'> Arkun, Y., & Yasemi, M. Dynamics and control of the ERK signaling pathway: Sensitivity, bistability, and oscillations. PloS one, 13(4), e0195513. doi: 10.1371/journal.pone.0195513 [https://doi.org/10.1371/journal.pone.0195513. DOI: 10.1371/journal.pone.0195513]. </Ref>
+For last sentence in implications van der Burgt <Ref name= 'van der Burgt'> van der Burgt, I. Noonan syndrome. Orphanet J Rare Dis 2, 4 (2007). doi: 10.1186/1750-1172-2-4 [https://doi.org/10.1186/1750-1172-2-4. DOI: 10.1186/1750-1172-2-4]. </Ref>
+PP1C REF: <Ref name= 'Aggen'> Aggen, J., Nairn, A., Chamberlin, R. Regulation of protein phosphatase-1. Chemistry & Biology 2000, 7:R13–R23. [https://www.cell.com/cell-chemical-biology/pdf/S1074-5521(00)00069-7.pdf]. </Ref>.
-== Biological Function ==
 == Relevance ==
@@ Line 17: / Line 46: @@
 This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
 </StructureSection>
 == References ==
 <references/>