1r8m

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (07:18, 30 October 2024) (edit) (undo)
 
(15 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1r8m.jpg|left|200px]]<br /><applet load="1r8m" size="350" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1r8m, resolution 1.70&Aring;" />
 
-
'''SEC7 DOMAIN OF THE ARF EXCHANGE FACTOR ARNO WITH BREFELDIN A-SENSITIZING MUTATIONS'''<br />
 
-
==Overview==
+
==SEC7 DOMAIN OF THE ARF EXCHANGE FACTOR ARNO WITH BREFELDIN A-SENSITIZING MUTATIONS==
-
Small GTP-binding (G) proteins are activated by GDP/GTP nucleotide, exchange stimulated by guanine nucleotide exchange factors (GEFs)., Nucleotide dissociation from small G protein-GEF complexes involves, transient GDP-bound intermediates whose structures have never been, described. In the case of Arf proteins, small G proteins that regulate, membrane traffic in eukaryotic cells, such intermediates can be trapped, either by the natural inhibitor brefeldin A or by charge reversal at the, catalytic glutamate of the Sec7 domain of their GEFs. Here we report the, crystal structures of these intermediates that show that membrane, recruitment of Arf and nucleotide dissociation are separate reactions, stimulated by Sec7. The reactions proceed through sequential rotations of, the Arf.GDP core towards the Sec7 catalytic site, and are blocked by, interfacial binding of brefeldin A and unproductive stabilization of GDP, by charge reversal. The structural characteristics of the reaction and its, modes of inhibition reveal unexplored ways in which to inhibit the, activation of small G proteins.
+
<StructureSection load='1r8m' size='340' side='right'caption='[[1r8m]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1r8m]] is a 1 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=1R8M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R8M FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
 +
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1r8m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r8m OCA], [https://pdbe.org/1r8m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r8m RCSB], [https://www.ebi.ac.uk/pdbsum/1r8m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r8m ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/CYH2_HUMAN CYH2_HUMAN] Acts as a guanine-nucleotide exchange factor (GEF). Promotes guanine-nucleotide exchange on ARF1, ARF3 and ARF6. Promotes the activation of ARF factors through replacement of GDP with GTP. The cell membrane form, in association with ARL4 proteins, recruits ARF6 to the plasma membrane.<ref>PMID:17398095</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/r8/1r8m_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1r8m ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Small GTP-binding (G) proteins are activated by GDP/GTP nucleotide exchange stimulated by guanine nucleotide exchange factors (GEFs). Nucleotide dissociation from small G protein-GEF complexes involves transient GDP-bound intermediates whose structures have never been described. In the case of Arf proteins, small G proteins that regulate membrane traffic in eukaryotic cells, such intermediates can be trapped either by the natural inhibitor brefeldin A or by charge reversal at the catalytic glutamate of the Sec7 domain of their GEFs. Here we report the crystal structures of these intermediates that show that membrane recruitment of Arf and nucleotide dissociation are separate reactions stimulated by Sec7. The reactions proceed through sequential rotations of the Arf.GDP core towards the Sec7 catalytic site, and are blocked by interfacial binding of brefeldin A and unproductive stabilization of GDP by charge reversal. The structural characteristics of the reaction and its modes of inhibition reveal unexplored ways in which to inhibit the activation of small G proteins.
-
==About this Structure==
+
Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor.,Renault L, Guibert B, Cherfils J Nature. 2003 Dec 4;426(6966):525-30. PMID:14654833<ref>PMID:14654833</ref>
-
1R8M is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MN:'>MN</scene> and <scene name='pdbligand=FMT:'>FMT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R8M OCA].
+
-
==Reference==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor., Renault L, Guibert B, Cherfils J, Nature. 2003 Dec 4;426(6966):525-30. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14654833 14654833]
+
</div>
 +
<div class="pdbe-citations 1r8m" style="background-color:#fffaf0;"></div>
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Single protein]]
+
[[Category: Large Structures]]
-
[[Category: Cherfils, J.]]
+
[[Category: Cherfils J]]
-
[[Category: Guibert, B.]]
+
[[Category: Guibert B]]
-
[[Category: Renault, L.]]
+
[[Category: Renault L]]
-
[[Category: FMT]]
+
-
[[Category: MN]]
+
-
[[Category: exchange factor]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:47:47 2008''
+

Current revision

SEC7 DOMAIN OF THE ARF EXCHANGE FACTOR ARNO WITH BREFELDIN A-SENSITIZING MUTATIONS

PDB ID 1r8m

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools