Sandbox Reserved 1777: Difference between revisions

Line 13:

==Overview==

The ~~protein~~ combines three separate ~~'''(see notes for more)'''. '''~~SHOC2, PP1C, and MRAS, to form the active protein (SMP complex)~~'''~~, as seen in Figure 2<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>. The SMP complex was determined via cryo-electron microscopy as well as x-ray diffraction. The overall architecture has PP1C and MRAS bound within the concave surface of SHOC2, leaving the catalytic site of PP1C and the GTP binding cleft in MRAS exposed.

The complex combines three separate proteins, SHOC2, PP1C, and MRAS, to form the active protein (SMP complex), as seen in Figure 2<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>. In complex, each of these proteins are responsible for a different role. MRAS is the "on and off" switch; when MRAS is activated from binding GTP, '''fill in here'''. PP1C by itself is a catalytic enzyme that ''' fill in here'''. In complex, PP1C is tasked with being the catalytic domain and removing a phosphate from RAF. The last piece of the complex is SHOC2, which is responsible for holding and stabilizing MRAS and PP1C <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>. The SMP complex was determined via cryo-electron microscopy as well as x-ray diffraction. The overall architecture has PP1C and MRAS bound within the concave surface of SHOC2, leaving the catalytic site of PP1C and the GTP binding cleft in MRAS exposed.

==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>]]

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 three signaling proteins. <scene name='95/952705/Shoc2_structure/2'>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/9'>LRR motifs</scene>. LRR motifs form an extended β-sheet on the inner concave surface of SHOC2 with α-helices facing outward to facilitate binding of the protein complex. These LRR motifs result in a largely hydrophobic core within the concave 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~~>.

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 three signaling proteins. <scene name='95/952705/Shoc2_structure/2'>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/9'>LRR motifs</scene>. LRR motifs form an extended β-sheet on the inner concave surface of SHOC2 with α-helices facing outward to facilitate binding of the protein complex. These LRR motifs result in a largely hydrophobic core within the concave region. <ref name="Hahn" />.

==PP1C==

<scene name='95/952705/Pp1c_structure/1'>PP1C</scene> is the catalytic domain of the phosphatase enzyme [https://www.ncbi.nlm.nih.gov/gene/5499 PP1], which removes reversible phosphorylations from signaling proteins. PP1C is a serine/threonine phosphatase involved in signaling pathways that control cell growth, division, and metabolism '''(REF)''' '''and explain more, see notes'''.

Sandbox Reserved 1777: Difference between revisions

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 13: / Line 13: @@
 ==Overview==
-The protein combines three separate '''(see notes for more)'''. '''SHOC2, PP1C, and MRAS, to form the active protein (SMP complex)''', as seen in Figure 2<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>. The SMP complex was determined via cryo-electron microscopy as well as x-ray diffraction. The overall architecture has PP1C and MRAS bound within the concave surface of SHOC2, leaving the catalytic site of PP1C and the GTP binding cleft in MRAS exposed.
+The complex combines three separate proteins, SHOC2, PP1C, and MRAS, to form the active protein (SMP complex), as seen in Figure 2<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>. In complex, each of these proteins are responsible for a different role. MRAS is the "on and off" switch; when MRAS is activated from binding GTP, '''fill in here'''. PP1C by itself is a catalytic enzyme that ''' fill in here'''. In complex, PP1C is tasked with being the catalytic domain and removing a phosphate from RAF. The last piece of the complex is SHOC2, which is responsible for holding and stabilizing MRAS and PP1C <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>. The SMP complex was determined via cryo-electron microscopy as well as x-ray diffraction. The overall architecture has PP1C and MRAS bound within the concave surface of SHOC2, leaving the catalytic site of PP1C and the GTP binding cleft in MRAS exposed.
 ==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>]]
-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 three signaling proteins. <scene name='95/952705/Shoc2_structure/2'>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/9'>LRR motifs</scene>. LRR motifs form an extended β-sheet on the inner concave surface of SHOC2 with α-helices facing outward to facilitate binding of the protein complex. These LRR motifs result in a largely hydrophobic core within the concave 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>.
+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 three signaling proteins. <scene name='95/952705/Shoc2_structure/2'>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/9'>LRR motifs</scene>. LRR motifs form an extended β-sheet on the inner concave surface of SHOC2 with α-helices facing outward to facilitate binding of the protein complex. These LRR motifs result in a largely hydrophobic core within the concave region. <ref name="Hahn" />.
 ==PP1C==
 <scene name='95/952705/Pp1c_structure/1'>PP1C</scene> is the catalytic domain of the phosphatase enzyme [https://www.ncbi.nlm.nih.gov/gene/5499 PP1], which removes reversible phosphorylations from signaling proteins. PP1C is a serine/threonine phosphatase involved in signaling pathways that control cell growth, division, and metabolism '''(REF)''' '''and explain more, see notes'''.