|
|
| Line 3: |
Line 3: |
| | <StructureSection load='1fzq' size='340' side='right'caption='[[1fzq]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='1fzq' size='340' side='right'caption='[[1fzq]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1fzq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FZQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FZQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1fzq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FZQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FZQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NH4:AMMONIUM+ION'>NH4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NH4:AMMONIUM+ION'>NH4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1fzq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fzq OCA], [https://pdbe.org/1fzq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fzq RCSB], [https://www.ebi.ac.uk/pdbsum/1fzq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fzq ProSAT]</span></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=1fzq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fzq OCA], [https://pdbe.org/1fzq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fzq RCSB], [https://www.ebi.ac.uk/pdbsum/1fzq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fzq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ARL3_MOUSE ARL3_MOUSE]] Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). Required for normal cytokinesis and cilia signaling. Required for targeting proteins such as NPHP3 to the ciliary membrane by releasing myristoylated NPHP3 from UNC119B cargo adapter into the cilium (By similarity). Requires assistance from GTPase-activating proteins (GAPs) like RP2 and PDE6D, in order to cycle between inactive GDP-bound and active GTP-bound forms.<ref>PMID:15979089</ref> <ref>PMID:18376416</ref>
| + | [https://www.uniprot.org/uniprot/ARL3_MOUSE ARL3_MOUSE] Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). Required for normal cytokinesis and cilia signaling. Required for targeting proteins such as NPHP3 to the ciliary membrane by releasing myristoylated NPHP3 from UNC119B cargo adapter into the cilium (By similarity). Requires assistance from GTPase-activating proteins (GAPs) like RP2 and PDE6D, in order to cycle between inactive GDP-bound and active GTP-bound forms.<ref>PMID:15979089</ref> <ref>PMID:18376416</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 33: |
Line 34: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Becker, J]] | + | [[Category: Becker J]] |
| - | [[Category: Hanzal-Bayer, M]] | + | [[Category: Hanzal-Bayer M]] |
| - | [[Category: Hillig, R C]] | + | [[Category: Hillig RC]] |
| - | [[Category: Linari, M]] | + | [[Category: Linari M]] |
| - | [[Category: Renault, L]] | + | [[Category: Renault L]] |
| - | [[Category: Wittinghofer, A]] | + | [[Category: Wittinghofer A]] |
| - | [[Category: Arf family]]
| + | |
| - | [[Category: G-domain]]
| + | |
| - | [[Category: Protein-gdp complex without magnesium]]
| + | |
| - | [[Category: Ras superfamily]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
ARL3_MOUSE Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). Required for normal cytokinesis and cilia signaling. Required for targeting proteins such as NPHP3 to the ciliary membrane by releasing myristoylated NPHP3 from UNC119B cargo adapter into the cilium (By similarity). Requires assistance from GTPase-activating proteins (GAPs) like RP2 and PDE6D, in order to cycle between inactive GDP-bound and active GTP-bound forms.[1] [2]
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
BACKGROUND: Based on sequence similarities, Arf-like (ARL) proteins have been assigned to the Arf subfamily of the superfamily of Ras-related GTP binding proteins. They have been identified in several isoforms in a wide variety of species. Their cellular function is unclear, but they are proposed to regulate intracellular transport. RESULTS: The 1.7 A crystal structure of murine ARL3-GDP provides a first insight into the structural features of this subgroup of Ar proteins. The N-terminal extension of ARL3 folds into an elongated loop region that is hydrophobically anchored onto the surface by burying 1440 A2. The features observed suggest that ARL3 releases its N terminus and undergoes a beta sheet register shift upon the binding of GTP. The structure and kinetic experiments with fluorescent mGDP demonstrate that tight GDP (but not GTP) binding is achieved in the absence of a magnesium ion. This is due to a lysine residue in the active site, close to the canonical Mg2+ site found in other GTP binding proteins. This is a distinct feature separating ARL2 and ARL3 from Arf proteins. CONCLUSION: The disturbed magnesium binding site and the independence of GDP coordination from the presence of Mg2+ separate ARL2 and ARL3 from Arf proteins. The D sheet register shift, which is similar to that of Arf, that is observed in the present structure, along with the postulated release of the N-terminal extension and the concomitant exposure of a patch of conserved hydrophobic residues in this region suggest that ARL proteins might be localized to target membranes upon exchange of GDP to GTP. Contrary to the situation in Arf, however, the conformational change to ARL-GTP does not require the presence of membranes and might thus be energetically unfavored. Together with the very low affinity described for the interaction of ARL3 with Mg-GTP, this suggests that ARL protein activation requires the presence of effectors stabilizing the GTP coordination rather than guanine nucleotide exchange factors (GEFs).
Structural and biochemical properties show ARL3-GDP as a distinct GTP binding protein.,Hillig RC, Hanzal-Bayer M, Linari M, Becker J, Wittinghofer A, Renault L Structure. 2000 Dec 15;8(12):1239-45. PMID:11188688[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hanzal-Bayer M, Linari M, Wittinghofer A. Properties of the interaction of Arf-like protein 2 with PDEdelta. J Mol Biol. 2005 Jul 29;350(5):1074-82. PMID:15979089 doi:10.1016/j.jmb.2005.05.036
- ↑ Veltel S, Gasper R, Eisenacher E, Wittinghofer A. The retinitis pigmentosa 2 gene product is a GTPase-activating protein for Arf-like 3. Nat Struct Mol Biol. 2008 Apr;15(4):373-80. Epub 2008 Mar 23. PMID:18376416 doi:nsmb.1396
- ↑ Hillig RC, Hanzal-Bayer M, Linari M, Becker J, Wittinghofer A, Renault L. Structural and biochemical properties show ARL3-GDP as a distinct GTP binding protein. Structure. 2000 Dec 15;8(12):1239-45. PMID:11188688
|
