1nvu: Difference between revisions

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{{Seed}}
[[Image:1nvu.png|left|200px]]


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==Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS==
The line below this paragraph, containing "STRUCTURE_1nvu", creates the "Structure Box" on the page.
<StructureSection load='1nvu' size='340' side='right'caption='[[1nvu]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[1nvu]] 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=1NVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NVU 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]] 2.2&#8491;</td></tr>
-->
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
{{STRUCTURE_1nvu|  PDB=1nvu  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nvu OCA], [https://pdbe.org/1nvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nvu RCSB], [https://www.ebi.ac.uk/pdbsum/1nvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nvu ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SOS1_HUMAN SOS1_HUMAN] Defects in SOS1 are the cause of gingival fibromatosis 1 (GGF1) [MIM:[https://omim.org/entry/135300 135300]; also known as GINGF1. Gingival fibromatosis is a rare overgrowth condition characterized by a benign, slowly progressive, nonhemorrhagic, fibrous enlargement of maxillary and mandibular keratinized gingiva. GGF1 is usually transmitted as an autosomal dominant trait, although sporadic cases are common.<ref>PMID:11868160</ref>  Defects in SOS1 are the cause of Noonan syndrome type 4 (NS4) [MIM:[https://omim.org/entry/610733 610733]. NS4 is an autosomal dominant disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births. Rarely, NS4 is associated with juvenile myelomonocytic leukemia (JMML). SOS1 mutations engender a high prevalence of pulmonary valve disease; atrial septal defects are less common.<ref>PMID:17143285</ref> <ref>PMID:17143282</ref> <ref>PMID:19020799</ref> <ref>PMID:19438935</ref> <ref>PMID:20683980</ref> <ref>PMID:20673819</ref> <ref>PMID:19953625</ref> <ref>PMID:21387466</ref>
== Function ==
[https://www.uniprot.org/uniprot/SOS1_HUMAN SOS1_HUMAN] Promotes the exchange of Ras-bound GDP by GTP.
== 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/1nvu_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=1nvu 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 1nvu" 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]]
-->
== 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==
1NVU is a 3 chains 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=1NVU OCA].
 
==Reference==
<ref group="xtra">PMID:12628188</ref><references group="xtra"/>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Bar-Sagi, D.]]
[[Category: Large Structures]]
[[Category: Hall, B E.]]
[[Category: Bar-Sagi D]]
[[Category: Hoelz, A.]]
[[Category: Hall BE]]
[[Category: Kuriyan, J.]]
[[Category: Hoelz A]]
[[Category: Margarit, S M.]]
[[Category: Kuriyan J]]
[[Category: Nagar, B.]]
[[Category: Margarit SM]]
[[Category: Pirruccello, M.]]
[[Category: Nagar B]]
[[Category: Sondermann, H.]]
[[Category: Pirruccello M]]
[[Category: Gtp binding]]
[[Category: Sondermann H]]
[[Category: Guanine nucleotide release factor]]
[[Category: Proto-oncogene]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 08:42:10 2009''

Latest revision as of 12:26, 16 August 2023

Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOSStructural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS

Structural highlights

1nvu is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SOS1_HUMAN Defects in SOS1 are the cause of gingival fibromatosis 1 (GGF1) [MIM:135300; also known as GINGF1. Gingival fibromatosis is a rare overgrowth condition characterized by a benign, slowly progressive, nonhemorrhagic, fibrous enlargement of maxillary and mandibular keratinized gingiva. GGF1 is usually transmitted as an autosomal dominant trait, although sporadic cases are common.[1] Defects in SOS1 are the cause of Noonan syndrome type 4 (NS4) [MIM:610733. NS4 is an autosomal dominant disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births. Rarely, NS4 is associated with juvenile myelomonocytic leukemia (JMML). SOS1 mutations engender a high prevalence of pulmonary valve disease; atrial septal defects are less common.[2] [3] [4] [5] [6] [7] [8] [9]

Function

SOS1_HUMAN Promotes the exchange of Ras-bound GDP by GTP.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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 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[10]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Hart TC, Zhang Y, Gorry MC, Hart PS, Cooper M, Marazita ML, Marks JM, Cortelli JR, Pallos D. A mutation in the SOS1 gene causes hereditary gingival fibromatosis type 1. Am J Hum Genet. 2002 Apr;70(4):943-54. Epub 2002 Feb 26. PMID:11868160 doi:S0002-9297(07)60301-2
  2. ↑ Roberts AE, Araki T, Swanson KD, Montgomery KT, Schiripo TA, Joshi VA, Li L, Yassin Y, Tamburino AM, Neel BG, Kucherlapati RS. Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nat Genet. 2007 Jan;39(1):70-4. Epub 2006 Dec 3. PMID:17143285 doi:ng1926
  3. ↑ Tartaglia M, Pennacchio LA, Zhao C, Yadav KK, Fodale V, Sarkozy A, Pandit B, Oishi K, Martinelli S, Schackwitz W, Ustaszewska A, Martin J, Bristow J, Carta C, Lepri F, Neri C, Vasta I, Gibson K, Curry CJ, Siguero JP, Digilio MC, Zampino G, Dallapiccola B, Bar-Sagi D, Gelb BD. Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nat Genet. 2007 Jan;39(1):75-9. Epub 2006 Dec 13. PMID:17143282 doi:10.1038/ng1939
  4. ↑ Ko JM, Kim JM, Kim GH, Yoo HW. PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome. J Hum Genet. 2008;53(11-12):999-1006. doi: 10.1007/s10038-008-0343-6. Epub 2008, Nov 20. PMID:19020799 doi:10.1007/s10038-008-0343-6
  5. ↑ Hanna N, Parfait B, Talaat IM, Vidaud M, Elsedfy HH. SOS1: a new player in the Noonan-like/multiple giant cell lesion syndrome. Clin Genet. 2009 Jun;75(6):568-71. doi: 10.1111/j.1399-0004.2009.01149.x. Epub, 2009 May 5. PMID:19438935 doi:10.1111/j.1399-0004.2009.01149.x
  6. ↑ Longoni M, Moncini S, Cisternino M, Morella IM, Ferraiuolo S, Russo S, Mannarino S, Brazzelli V, Coi P, Zippel R, Venturin M, Riva P. Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations. Am J Med Genet A. 2010 Sep;152A(9):2176-84. doi: 10.1002/ajmg.a.33564. PMID:20683980 doi:10.1002/ajmg.a.33564
  7. ↑ Fabretto A, Kutsche K, Harmsen MB, Demarini S, Gasparini P, Fertz MC, Zenker M. Two cases of Noonan syndrome with severe respiratory and gastroenteral involvement and the SOS1 mutation F623I. Eur J Med Genet. 2010 Sep-Oct;53(5):322-4. doi: 10.1016/j.ejmg.2010.07.011. Epub , 2010 Jul 29. PMID:20673819 doi:10.1016/j.ejmg.2010.07.011
  8. ↑ Denayer E, Devriendt K, de Ravel T, Van Buggenhout G, Smeets E, Francois I, Sznajer Y, Craen M, Leventopoulos G, Mutesa L, Vandecasseye W, Massa G, Kayserili H, Sciot R, Fryns JP, Legius E. Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations. Genes Chromosomes Cancer. 2010 Mar;49(3):242-52. doi: 10.1002/gcc.20735. PMID:19953625 doi:10.1002/gcc.20735
  9. ↑ Lepri F, De Luca A, Stella L, Rossi C, Baldassarre G, Pantaleoni F, Cordeddu V, Williams BJ, Dentici ML, Caputo V, Venanzi S, Bonaguro M, Kavamura I, Faienza MF, Pilotta A, Stanzial F, Faravelli F, Gabrielli O, Marino B, Neri G, Silengo MC, Ferrero GB, Torrrente I, Selicorni A, Mazzanti L, Digilio MC, Zampino G, Dallapiccola B, Gelb BD, Tartaglia M. SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype-phenotype correlations. Hum Mutat. 2011 Jul;32(7):760-72. doi: 10.1002/humu.21492. Epub 2011 Apr 28. PMID:21387466 doi:10.1002/humu.21492
  10. ↑ Margarit SM, Sondermann H, Hall BE, Nagar B, Hoelz A, Pirruccello M, Bar-Sagi D, Kuriyan J. Structural evidence for feedback activation by Ras.GTP of the Ras-specific nucleotide exchange factor SOS. Cell. 2003 Mar 7;112(5):685-95. PMID:12628188

1nvu, resolution 2.20Å

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