1gua: Difference between revisions

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[[Image:1gua.gif|left|200px]]<br />

[[Image:1gua.gif|left|200px]]<br /><applet load="1gua" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="1gua" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1gua, resolution 2.0Å" />

'''HUMAN RAP1A, RESIDUES 1-167, DOUBLE MUTANT (E30D,K31E) COMPLEXED WITH GPPNHP AND THE RAS-BINDING-DOMAIN OF HUMAN C-RAF1, RESIDUES 51-131'''<br />

==Overview==

Members of the Ras subfamily of small GTP-binding proteins have been shown, to be promiscuous towards a variety of putative effector molecules such as, the protein kinase c-Raf and the Ral-specific guanine nucleotide exchange, factor (Ral-GEF). To address the question of specificity of interactions, we have introduced the mutations E30D and K31E into Rap and show, biochemically, by X-ray structure analysis and by transfection in vivo, that the identical core effector region of Ras and Rap (residues 32-40) is, responsible for molecular recognition, but that residues outside this, region are responsible for the specificity of the interaction. The major, determinant for the switch in specificity is the opposite charge of, residue 31--Lys in Rap, Glu in Ras--which creates a favourable, complementary interface for the Ras-Raf interaction.

Members of the Ras subfamily of small GTP-binding proteins have been shown to be promiscuous towards a variety of putative effector molecules such as the protein kinase c-Raf and the Ral-specific guanine nucleotide exchange factor (Ral-GEF). To address the question of specificity of interactions we have introduced the mutations E30D and K31E into Rap and show biochemically, by X-ray structure analysis and by transfection in vivo that the identical core effector region of Ras and Rap (residues 32-40) is responsible for molecular recognition, but that residues outside this region are responsible for the specificity of the interaction. The major determinant for the switch in specificity is the opposite charge of residue 31--Lys in Rap, Glu in Ras--which creates a favourable complementary interface for the Ras-Raf interaction.

==Disease==

Known diseases associated with this structure: LEOPARD syndrome 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164760 164760]], Noonan syndrome 5 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164760 164760]]

==About this Structure==

1GUA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG, CA and GNP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1GUA OCA].

1GUA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=GNP:'>GNP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GUA OCA].

==Reference==

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[[Category: oncogene protein/kinase/effector protein gtp-binding-protein]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov~~ 12 17:09:~~07 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:54:05 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1gua.gif|left|200px]]<br />
+[[Image:1gua.gif|left|200px]]<br /><applet load="1gua" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1gua" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1gua, resolution 2.0&Aring;" />
 '''HUMAN RAP1A, RESIDUES 1-167, DOUBLE MUTANT (E30D,K31E) COMPLEXED WITH GPPNHP AND THE RAS-BINDING-DOMAIN OF HUMAN C-RAF1, RESIDUES 51-131'''<br />
 ==Overview==
-Members of the Ras subfamily of small GTP-binding proteins have been shown, to be promiscuous towards a variety of putative effector molecules such as, the protein kinase c-Raf and the Ral-specific guanine nucleotide exchange, factor (Ral-GEF). To address the question of specificity of interactions, we have introduced the mutations E30D and K31E into Rap and show, biochemically, by X-ray structure analysis and by transfection in vivo, that the identical core effector region of Ras and Rap (residues 32-40) is, responsible for molecular recognition, but that residues outside this, region are responsible for the specificity of the interaction. The major, determinant for the switch in specificity is the opposite charge of, residue 31--Lys in Rap, Glu in Ras--which creates a favourable, complementary interface for the Ras-Raf interaction.
+Members of the Ras subfamily of small GTP-binding proteins have been shown to be promiscuous towards a variety of putative effector molecules such as the protein kinase c-Raf and the Ral-specific guanine nucleotide exchange factor (Ral-GEF). To address the question of specificity of interactions we have introduced the mutations E30D and K31E into Rap and show biochemically, by X-ray structure analysis and by transfection in vivo that the identical core effector region of Ras and Rap (residues 32-40) is responsible for molecular recognition, but that residues outside this region are responsible for the specificity of the interaction. The major determinant for the switch in specificity is the opposite charge of residue 31--Lys in Rap, Glu in Ras--which creates a favourable complementary interface for the Ras-Raf interaction.
+==Disease==
+Known diseases associated with this structure: LEOPARD syndrome 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164760 164760]], Noonan syndrome 5 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164760 164760]]
 ==About this Structure==
-GUA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG, CA and GNP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GUA OCA].
+GUA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=GNP:'>GNP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GUA OCA].
 ==Reference==
@@ Line 22: / Line 24: @@
 [[Category: oncogene protein/kinase/effector protein gtp-binding-protein]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:09:07 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:54:05 2008''