Sandbox Reserved 1706: Difference between revisions

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Mutations to the arginine finger are shown to slow function of NF1 and other GTPases in their function in accelerating GTP hydrolysis. When a Ras GAP such as NF1 can functionally utilize its arginine finger, it allows NF1 to rapidly hydrolyze GTP when bound to Ras. This emphasizes the importance of the R1276 residue for the GRD site binding to Ras.<ref name="Bourne"> DOI:10.1038/39470</ref><ref name="Lupton"> DOI:10.1038/s41594-021-00687-2</ref><ref name="Naschberger"> DOI:10.1038/s41586-021-04024-x</ref>

==SPRED 1==

SPRED 1 is a protein that binds to the GAPex domain of Neurofibromin. Its function recruits the Neurofibromin protein when bound from the cytosol to the plasma membrane. SPRED 1 will bind to the GAPex domain of Neurofibromin in the <scene name='90/904311/Sped-1_closed/1'>closed conformation'</scene> in the cytosol to recruit Neurofibromin to the plasma membrane. Unlike Ras, SPRED-1 does show the ability to <scene name='90/904311/Spred-1_open/1'>bind to the open conformation</scene>. When bound to the open conformation of Neurofibromin in the cytosol, it may present a different orientation that impacts the recruitment to the plasma membrane. Further research is needed to assess the impact of the function and the changes it may present.

SPRED 1 is a protein that binds to the GAPex domain of Neurofibromin. Its function recruits the Neurofibromin protein when bound from the cytosol to the plasma membrane. SPRED 1 will bind to the GAPex domain of Neurofibromin in the <scene name='90/904311/Sped-1_closed/1'>closed conformation'</scene> in the cytosol to recruit Neurofibromin to the plasma membrane. Unlike Ras, SPRED-1 does show the ability to <scene name='90/904311/Spred-1_open/1'>bind to the open conformation</scene>. When bound to the open conformation of Neurofibromin in the cytosol, it may present a different orientation that impacts the recruitment to the plasma membrane. Further research is needed to assess the impact of the function and the changes it may present.<ref name="Lupton"> DOI:10.1038/s41594-021-00687-2</ref><ref name="Naschberger"> DOI:10.1038/s41586-021-04024-x</ref>

==Future Clinical Relevance==

[https://en.wikipedia.org/wiki/Germline_mutation Germline mutations] are common in NF1, often causing genetic tumor syndrome through misregulation of the Ras signaling pathway. [https://en.wikipedia.org/wiki/Somatic_mutation Somatic mutations] among NF1 are also extremely common. In germline mutations and some somatic mutations of NF1, clinical findings show tumors that develop often along the deep epidermis layer of the skin. The most common among NF1 mutations is [https://en.wikipedia.org/wiki/Neurofibroma Neurofibroma]. Physically, soft skin-colored pink papules develop on the extremities or on the neck. Also in patients they become prevalent during puberty. Among germline mutations Neurofibroma seems to be the most well known, other tumors may also be common. [https://en.wikipedia.org/wiki/Lisch_nodule Lisch Nodules] are also common in the development of [https://en.wikipedia.org/wiki/Melanoma melanoma] within melanocytes as a result of NF1 mutations. Plexiform Neurofibroma and [https://en.wikipedia.org/wiki/Glaucoma Optic Glioma] also are tumor based syndromes resulting from these germline mutations. Increased risk in cancer for patients with mutations to NF1 is about 4 fold greater. Treatment options do exist for patients involving a multitude of drug based treatments coupled with chemotherapy. Surgery and laser treatments are also common.

Sandbox Reserved 1706: Difference between revisions

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@@ Line 42: / Line 42: @@
 Mutations to the arginine finger are shown to slow function of NF1 and other GTPases in their function in accelerating GTP hydrolysis. When a Ras GAP such as NF1 can functionally utilize its arginine finger, it allows NF1 to rapidly hydrolyze GTP when bound to Ras. This emphasizes the importance of the R1276 residue for the GRD site binding to Ras.<ref name="Bourne"> DOI:10.1038/39470</ref><ref name="Lupton"> DOI:10.1038/s41594-021-00687-2</ref><ref name="Naschberger"> DOI:10.1038/s41586-021-04024-x</ref>
 ==SPRED 1==
-SPRED 1 is a protein that binds to the GAPex domain of Neurofibromin. Its function recruits the Neurofibromin protein when bound from the cytosol to the plasma membrane. SPRED 1 will bind to the GAPex domain of Neurofibromin in the <scene name='90/904311/Sped-1_closed/1'>closed conformation'</scene> in the cytosol to recruit Neurofibromin to the plasma membrane. Unlike Ras, SPRED-1 does show the ability to <scene name='90/904311/Spred-1_open/1'>bind to the open conformation</scene>. When bound to the open conformation of Neurofibromin in the cytosol, it may present a different orientation that impacts the recruitment to the plasma membrane. Further research is needed to assess the impact of the function and the changes it may present.
+SPRED 1 is a protein that binds to the GAPex domain of Neurofibromin. Its function recruits the Neurofibromin protein when bound from the cytosol to the plasma membrane. SPRED 1 will bind to the GAPex domain of Neurofibromin in the <scene name='90/904311/Sped-1_closed/1'>closed conformation'</scene> in the cytosol to recruit Neurofibromin to the plasma membrane. Unlike Ras, SPRED-1 does show the ability to <scene name='90/904311/Spred-1_open/1'>bind to the open conformation</scene>. When bound to the open conformation of Neurofibromin in the cytosol, it may present a different orientation that impacts the recruitment to the plasma membrane. Further research is needed to assess the impact of the function and the changes it may present.<ref name="Lupton"> DOI:10.1038/s41594-021-00687-2</ref><ref name="Naschberger"> DOI:10.1038/s41586-021-04024-x</ref>
 ==Future Clinical Relevance==
 [https://en.wikipedia.org/wiki/Germline_mutation Germline mutations] are common in NF1, often causing genetic tumor syndrome through misregulation of the Ras signaling pathway. [https://en.wikipedia.org/wiki/Somatic_mutation Somatic mutations] among NF1 are also extremely common. In germline mutations and some somatic mutations of NF1, clinical findings show tumors that develop often along the deep epidermis layer of the skin. The most common among NF1 mutations is [https://en.wikipedia.org/wiki/Neurofibroma Neurofibroma]. Physically, soft skin-colored pink papules develop on the extremities or on the neck. Also in patients they become prevalent during puberty. Among germline mutations Neurofibroma seems to be the most well known, other tumors may also be common. [https://en.wikipedia.org/wiki/Lisch_nodule Lisch Nodules] are also common in the development of [https://en.wikipedia.org/wiki/Melanoma melanoma] within melanocytes as a result of NF1 mutations. Plexiform Neurofibroma and [https://en.wikipedia.org/wiki/Glaucoma Optic Glioma] also are tumor based syndromes resulting from these germline mutations. Increased risk in cancer for patients with mutations to NF1 is about 4 fold greater. Treatment options do exist for patients involving a multitude of drug based treatments coupled with chemotherapy. Surgery and laser treatments are also common.