1nvw: Difference between revisions

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[[Image:1nvw.png|left|200px]]


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==Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS==
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<StructureSection load='1nvw' size='340' side='right'caption='[[1nvw]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[1nvw]] is a 3 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=1NVW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NVW FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
{{STRUCTURE_1nvw|  PDB=1nvw  |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nvw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nvw OCA], [https://pdbe.org/1nvw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nvw RCSB], [https://www.ebi.ac.uk/pdbsum/1nvw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nvw ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/RASH_HUMAN RASH_HUMAN] Defects in HRAS are the cause of faciocutaneoskeletal syndrome (FCSS) [MIM:[https://omim.org/entry/218040 218040]. A rare condition characterized by prenatally increased growth, postnatal growth deficiency, mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities.<ref>PMID:16170316</ref> <ref>PMID:16329078</ref> <ref>PMID:16443854</ref> <ref>PMID:17054105</ref> <ref>PMID:18247425</ref> <ref>PMID:18039947</ref> <ref>PMID:19995790</ref>  Defects in HRAS are the cause of congenital myopathy with excess of muscle spindles (CMEMS) [MIM:[https://omim.org/entry/218040 218040]. CMEMS is a variant of Costello syndrome.<ref>PMID:17412879</ref>  Defects in HRAS may be a cause of susceptibility to Hurthle cell thyroid carcinoma (HCTC) [MIM:[https://omim.org/entry/607464 607464]. Hurthle cell thyroid carcinoma accounts for approximately 3% of all thyroid cancers. Although they are classified as variants of follicular neoplasms, they are more often multifocal and somewhat more aggressive and are less likely to take up iodine than are other follicular neoplasms.  Note=Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors.  Defects in HRAS are a cause of susceptibility to bladder cancer (BLC) [MIM:[https://omim.org/entry/109800 109800]. A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas. They begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences.  Note=Defects in HRAS are the cause of oral squamous cell carcinoma (OSCC).<ref>PMID:1459726</ref>  Defects in HRAS are the cause of Schimmelpenning-Feuerstein-Mims syndrome (SFM) [MIM:[https://omim.org/entry/163200 163200]. A disease characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects. Many oral manifestations have been reported, not only including hypoplastic and malformed teeth, and mucosal papillomatosis, but also ankyloglossia, hemihyperplastic tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous nevi follow the lines of Blaschko and these can continue as linear intraoral lesions, as in mucosal papillomatosis.<ref>PMID:22683711</ref>
== Function ==
[https://www.uniprot.org/uniprot/RASH_HUMAN RASH_HUMAN] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.<ref>PMID:14500341</ref> <ref>PMID:9020151</ref> <ref>PMID:12740440</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nv/1nvw_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=1nvw ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Growth factor receptors activate Ras by recruiting the nucleotide exchange factor son of sevenless (SOS) to the cell membrane, thereby triggering the production of GTP-loaded Ras. Crystallographic analyses of Ras bound to the catalytic module of SOS have led to the unexpected discovery of a highly conserved Ras binding site on SOS that is located distal to the active site and is specific for Ras.GTP. The crystal structures suggest that Ras.GTP stabilizes the active site of SOS allosterically, and we show that Ras.GTP forms ternary complexes with SOS(cat) in solution and increases significantly the rate of SOS(cat)-stimulated nucleotide release from Ras. These results demonstrate the existence of a positive feedback mechanism for the spatial and temporal regulation of Ras.


===Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS===
Structural evidence for feedback activation by Ras.GTP of the Ras-specific nucleotide exchange factor SOS.,Margarit SM, Sondermann H, Hall BE, Nagar B, Hoelz A, Pirruccello M, Bar-Sagi D, Kuriyan J Cell. 2003 Mar 7;112(5):685-95. PMID:12628188<ref>PMID:12628188</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1nvw" style="background-color:#fffaf0;"></div>


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==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_12628188}}, adds the Publication Abstract to the page
*[[GTPase Hras 3D structures|GTPase Hras 3D structures]]
(as it appears on PubMed at http://www.pubmed.gov), where 12628188 is the PubMed ID number.
*[[Son of sevenless|Son of sevenless]]
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== References ==
{{ABSTRACT_PUBMED_12628188}}
<references/>
 
__TOC__
==Disease==
</StructureSection>
Known disease associated with this structure: Fibromatosis, gingival OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=182530 182530]], Noonan syndrome 4 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=182530 182530]]
 
==About this Structure==
1NVW is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NVW OCA].
 
==Reference==
Structural evidence for feedback activation by Ras.GTP of the Ras-specific nucleotide exchange factor SOS., Margarit SM, Sondermann H, Hall BE, Nagar B, Hoelz A, Pirruccello M, Bar-Sagi D, Kuriyan J, Cell. 2003 Mar 7;112(5):685-95. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12628188 12628188]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Bar-Sagi, D.]]
[[Category: Bar-Sagi D]]
[[Category: Hall, B E.]]
[[Category: Hall BE]]
[[Category: Hoelz, A.]]
[[Category: Hoelz A]]
[[Category: Kuriyan, J.]]
[[Category: Kuriyan J]]
[[Category: Margarit, S M.]]
[[Category: Margarit SM]]
[[Category: Nagar, B.]]
[[Category: Nagar B]]
[[Category: Pirruccello, M.]]
[[Category: Pirruccello M]]
[[Category: Sondermann, H.]]
[[Category: Sondermann H]]
[[Category: Gtp-binding]]
[[Category: Guanine-nucleotide releasing factor]]
[[Category: Proto-oncogene]]
 
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