5kut: Difference between revisions
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==hMiro2 C-terminal GTPase domain, GDP-bound== | |||
<StructureSection load='5kut' size='340' side='right' caption='[[5kut]], [[Resolution|resolution]] 1.69Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5kut]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KUT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KUT FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kso|5kso]], [[5ksp|5ksp]], [[5ksy|5ksy]], [[5ksz|5ksz]], [[5kty|5kty]], [[5ku1|5ku1]]</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5kut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kut OCA], [http://pdbe.org/5kut PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kut RCSB], [http://www.ebi.ac.uk/pdbsum/5kut PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kut ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/MIRO2_HUMAN MIRO2_HUMAN]] Mitochondrial GTPase involved in mitochondrial trafficking. Probably involved in control of anterograde transport of mitochondria and their subcellular distribution (By similarity).<ref>PMID:16630562</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Hereditary Parkinson's disease is commonly caused by mutations in the protein kinase PINK1 or the E3 ubiquitin ligase Parkin, which function together to eliminate damaged mitochondria. PINK1 phosphorylates both Parkin and ubiquitin to stimulate ubiquitination of dozens of proteins on the surface of the outer mitochondrial membrane. However, the mechanisms by which Parkin recognizes specific proteins for modification remain largely unexplored. Here, we show that the C-terminal GTPase (cGTPase) of the Parkin primary substrate human Miro is necessary and sufficient for efficient ubiquitination. We present several new X-ray crystal structures of both human Miro1 and Miro2 that reveal substrate recognition and ubiquitin transfer to be specific to particular protein domains and lysine residues. We also provide evidence that Parkin substrate recognition is functionally separate from substrate modification. Finally, we show that prioritization for modification of a specific lysine sidechain of the cGTPase (K572) within human Miro1 is dependent on both its location and chemical microenvironment. Activation of Parkin by phosphorylation or by binding of pUb is required for prioritization of K572 for modification, suggesting that Parkin activation and acquisition of substrate specificity are coupled. | |||
Structural insights into Parkin substrate lysine targeting from minimal Miro substrates.,Klosowiak JL, Park S, Smith KP, French ME, Focia PJ, Freymann DM, Rice SE Sci Rep. 2016 Sep 8;6:33019. doi: 10.1038/srep33019. PMID:27605430<ref>PMID:27605430</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Freymann, D | <div class="pdbe-citations 5kut" style="background-color:#fffaf0;"></div> | ||
[[Category: Rice, S | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Focia, P J]] | |||
[[Category: Freymann, D M]] | |||
[[Category: Klosowiak, J L]] | |||
[[Category: Rice, S E]] | |||
[[Category: Gtpase]] | |||
[[Category: Hydrolase]] | |||
[[Category: Miro]] | |||
[[Category: Mitochondria]] | |||
[[Category: Parkin]] | |||
Revision as of 16:57, 21 September 2016
hMiro2 C-terminal GTPase domain, GDP-boundhMiro2 C-terminal GTPase domain, GDP-bound
Structural highlights
Function[MIRO2_HUMAN] Mitochondrial GTPase involved in mitochondrial trafficking. Probably involved in control of anterograde transport of mitochondria and their subcellular distribution (By similarity).[1] Publication Abstract from PubMedHereditary Parkinson's disease is commonly caused by mutations in the protein kinase PINK1 or the E3 ubiquitin ligase Parkin, which function together to eliminate damaged mitochondria. PINK1 phosphorylates both Parkin and ubiquitin to stimulate ubiquitination of dozens of proteins on the surface of the outer mitochondrial membrane. However, the mechanisms by which Parkin recognizes specific proteins for modification remain largely unexplored. Here, we show that the C-terminal GTPase (cGTPase) of the Parkin primary substrate human Miro is necessary and sufficient for efficient ubiquitination. We present several new X-ray crystal structures of both human Miro1 and Miro2 that reveal substrate recognition and ubiquitin transfer to be specific to particular protein domains and lysine residues. We also provide evidence that Parkin substrate recognition is functionally separate from substrate modification. Finally, we show that prioritization for modification of a specific lysine sidechain of the cGTPase (K572) within human Miro1 is dependent on both its location and chemical microenvironment. Activation of Parkin by phosphorylation or by binding of pUb is required for prioritization of K572 for modification, suggesting that Parkin activation and acquisition of substrate specificity are coupled. Structural insights into Parkin substrate lysine targeting from minimal Miro substrates.,Klosowiak JL, Park S, Smith KP, French ME, Focia PJ, Freymann DM, Rice SE Sci Rep. 2016 Sep 8;6:33019. doi: 10.1038/srep33019. PMID:27605430[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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