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From Proteopedia
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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. | 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> | ||
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| + | Hauseman<ref name="Hauseman" /> | ||
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| + | Kwon <Ref name='Kwan'>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> | ||
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| + | 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> | ||
== Relevance == | == Relevance == | ||
Revision as of 20:13, 27 March 2023
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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.
- ↑ 3.0 3.1 3.2 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.
- ↑ 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. DOI:10.1038/s41586-022-04838-3.
- ↑ 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.
- ↑ 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.
