2d4q
From Proteopedia
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==Crystal structure of the Sec-PH domain of the human neurofibromatosis type 1 protein== | ==Crystal structure of the Sec-PH domain of the human neurofibromatosis type 1 protein== | ||
| - | <StructureSection load='2d4q' size='340' side='right' caption='[[2d4q]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='2d4q' size='340' side='right'caption='[[2d4q]], [[Resolution|resolution]] 2.30Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[2d4q]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[2d4q]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D4Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2D4Q FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OXN:OXTOXYNOL-10'>OXN</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2d4q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2d4q OCA], [https://pdbe.org/2d4q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2d4q RCSB], [https://www.ebi.ac.uk/pdbsum/2d4q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2d4q ProSAT]</span></td></tr> |
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/NF1_HUMAN NF1_HUMAN] Defects in NF1 are the cause of neurofibromatosis type 1 (NF1) [MIM:[https://omim.org/entry/162200 162200]; also known as von Recklinghausen syndrome. A disease characterized by patches of skin pigmentation (cafe-au-lait spots), Lisch nodules of the iris, tumors in the peripheral nervous system and fibromatous skin tumors. Individuals with the disorder have increased susceptibility to the development of benign and malignant tumors.<ref>PMID:2114220</ref> <ref>PMID:1302608</ref> <ref>PMID:7981679</ref> <ref>PMID:8081387</ref> <ref>PMID:8544190</ref> <ref>PMID:8834249</ref> <ref>PMID:8807336</ref> <ref>PMID:9003501</ref> <ref>PMID:9150739</ref> <ref>PMID:9101300</ref> <ref>PMID:9298829</ref> <ref>PMID:9668168</ref> <ref>PMID:10336779</ref> <ref>PMID:11258625</ref> <ref>PMID:10220149</ref> <ref>PMID:10712197</ref> <ref>PMID:10607834</ref> <ref>PMID:10980545</ref> <ref>PMID:11735023</ref> <ref>PMID:11857752</ref> <ref>PMID:12522551</ref> <ref>PMID:12552569</ref> <ref>PMID:12746402</ref> <ref>PMID:15523642</ref> <ref>PMID:15146469</ref> <ref>PMID:15060124</ref> <ref>PMID:15520408</ref> <ref>PMID:15948193</ref> <ref>PMID:21838856</ref> Defects in NF1 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[https://omim.org/entry/607785 607785]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. Germline mutations of NF1 account for the association of JMML with type 1 neurofibromatosis (NF1). Defects in NF1 are the cause of Watson syndrome (WS) [MIM:[https://omim.org/entry/193520 193520]. WS is characterized by the presence of pulmonary stenosis, cafe-au-lait spots, and mental retardation. WS is considered as an atypical form of NF1. Defects in NF1 are a cause of familial spinal neurofibromatosis (FSNF) [MIM:[https://omim.org/entry/162210 162210]. Familial spinal NF is considered to be an alternative form of neurofibromatosis, showing multiple spinal tumors.<ref>PMID:11704931</ref> Defects in NF1 are a cause of neurofibromatosis-Noonan syndrome (NFNS) [MIM:[https://omim.org/entry/601321 601321]. NFNS is characterized by manifestations of both NF1 and Noonan syndrome (NS). NS is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis.<ref>PMID:12707950</ref> <ref>PMID:16380919</ref> <ref>PMID:19845691</ref> Defects in NF1 may be a cause of colorectal cancer (CRC) [MIM:[https://omim.org/entry/114500 114500]. |
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/NF1_HUMAN NF1_HUMAN] Stimulates the GTPase activity of Ras. NF1 shows greater affinity for Ras GAP, but lower specific activity. May be a regulator of Ras activity.<ref>PMID:2121371</ref> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2d4q ConSurf]. | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2d4q ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Neurofibromatosis type 1 (NF1) is a common tumour predisposition syndrome associated with numerous clinical complications. Mutations in the tumour suppressor gene NF1 are responsible for disease pathogenesis. This gene encodes the 320 kDa protein neurofibromin, the only clearly defined function of which is to act as a Ras-specific GTPase-activating protein (RasGAP). Here we report the structural discovery of a novel module in neurofibromin, composed of a Sec14p homologous segment and a previously undetected pleckstrin homology (PH)-like domain of potentially novel function. We show phospholipid binding by this bipartite module and identify residues that are involved in this activity; we also show that the PH-like domain is not sufficient for lipid binding. The unique architecture of the domain interface points to a model of how the PH-like domain may regulate binding of a ligand by the Sec14 module. | ||
| - | + | ==See Also== | |
| - | + | *[[Neurofibromin|Neurofibromin]] | |
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== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Bonneau F]] |
| - | [[Category: | + | [[Category: D'angelo I]] |
| - | + | [[Category: Scheffzek K]] | |
| - | [[Category: | + | [[Category: Welti S]] |
| - | [[Category: | + | |
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Current revision
Crystal structure of the Sec-PH domain of the human neurofibromatosis type 1 protein
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