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| | ==Structure of human Rab10 in complex with the bMERB domain of Mical-1== | | ==Structure of human Rab10 in complex with the bMERB domain of Mical-1== |
| - | <StructureSection load='5lpn' size='340' side='right' caption='[[5lpn]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='5lpn' size='340' side='right'caption='[[5lpn]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5lpn]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LPN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LPN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5lpn]] 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=5LPN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LPN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.8Å</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=5lpn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lpn OCA], [http://pdbe.org/5lpn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lpn RCSB], [http://www.ebi.ac.uk/pdbsum/5lpn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lpn ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=5lpn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lpn OCA], [https://pdbe.org/5lpn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lpn RCSB], [https://www.ebi.ac.uk/pdbsum/5lpn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lpn ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RAB10_HUMAN RAB10_HUMAN]] The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). That Rab is mainly involved in the biosynthetic transport of proteins from the Golgi to the plasma membrane. Regulates, for instance, SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane. In parallel, it regulates the transport of TLR4, a toll-like receptor to the plasma membrane and therefore may be important for innate immune response. Plays also a specific role in asymmetric protein transport to the plasma membrane within the polarized neuron and epithelial cells. In neurons, it is involved in axonogenesis through regulation of vesicular membrane trafficking toward the axonal plasma membrane while in epithelial cells, it regulates transport from the Golgi to the basolateral membrane. Moreover, may play a role in the basolateral recycling pathway and in phagosome maturation. According to PubMed:23263280, may play a role in endoplasmic reticulum dynamics and morphology controlling tubulation along microtubules and tubules fusion.<ref>PMID:16641372</ref> <ref>PMID:21248164</ref> <ref>PMID:23263280</ref> [[http://www.uniprot.org/uniprot/MICA1_HUMAN MICA1_HUMAN]] Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin. Acts by modifying actin subunits through the addition of oxygen to form methionine-sulfoxide, leading to promote actin filament severing and prevent repolymerization (Probable). Acts as a cytoskeletal regulator that connects NEDD9 to intermediate filaments. Also acts as a negative regulator of apoptosis via its interaction with STK38 and STK38L; acts by antagonizing STK38 and STK38L activation by MST1/STK4.<ref>PMID:18305261</ref> <ref>PMID:21864500</ref> | + | [https://www.uniprot.org/uniprot/RAB10_HUMAN RAB10_HUMAN] The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). That Rab is mainly involved in the biosynthetic transport of proteins from the Golgi to the plasma membrane. Regulates, for instance, SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane. In parallel, it regulates the transport of TLR4, a toll-like receptor to the plasma membrane and therefore may be important for innate immune response. Plays also a specific role in asymmetric protein transport to the plasma membrane within the polarized neuron and epithelial cells. In neurons, it is involved in axonogenesis through regulation of vesicular membrane trafficking toward the axonal plasma membrane while in epithelial cells, it regulates transport from the Golgi to the basolateral membrane. Moreover, may play a role in the basolateral recycling pathway and in phagosome maturation. According to PubMed:23263280, may play a role in endoplasmic reticulum dynamics and morphology controlling tubulation along microtubules and tubules fusion.<ref>PMID:16641372</ref> <ref>PMID:21248164</ref> <ref>PMID:23263280</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5lpn" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5lpn" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ras-related protein Rab 3D structures|Ras-related protein Rab 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Campos, J]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Friese, T]] | + | [[Category: Large Structures]] |
| - | [[Category: Fu, Y]] | + | [[Category: Campos J]] |
| - | [[Category: Gazdag, E M]] | + | [[Category: Friese T]] |
| - | [[Category: Goody, R S]] | + | [[Category: Fu Y]] |
| - | [[Category: Itzen, A]] | + | [[Category: Gazdag EM]] |
| - | [[Category: Mueller, M P]] | + | [[Category: Goody RS]] |
| - | [[Category: Oprisko, A]] | + | [[Category: Itzen A]] |
| - | [[Category: Rai, A]] | + | [[Category: Mueller MP]] |
| - | [[Category: Duf3585]]
| + | [[Category: Oprisko A]] |
| - | [[Category: Endocytosis]]
| + | [[Category: Rai A]] |
| - | [[Category: Mical]]
| + | |
| - | [[Category: Mical-1]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Rab effector]]
| + | |
| - | [[Category: Rab10]]
| + | |
| Structural highlights
Function
RAB10_HUMAN The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). That Rab is mainly involved in the biosynthetic transport of proteins from the Golgi to the plasma membrane. Regulates, for instance, SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane. In parallel, it regulates the transport of TLR4, a toll-like receptor to the plasma membrane and therefore may be important for innate immune response. Plays also a specific role in asymmetric protein transport to the plasma membrane within the polarized neuron and epithelial cells. In neurons, it is involved in axonogenesis through regulation of vesicular membrane trafficking toward the axonal plasma membrane while in epithelial cells, it regulates transport from the Golgi to the basolateral membrane. Moreover, may play a role in the basolateral recycling pathway and in phagosome maturation. According to PubMed:23263280, may play a role in endoplasmic reticulum dynamics and morphology controlling tubulation along microtubules and tubules fusion.[1] [2] [3]
Publication Abstract from PubMed
In their active GTP-bound form, Rab proteins interact with proteins termed effector molecules. In this study we have thoroughly characterised a Rab effector domain that is present in proteins of the Mical and EHBP families, both known to act in endosomal trafficking. Within our study, we show that these effectors display a preference for Rab8 family proteins (Rab8, 10, 13 and 15) and that some of the effector domains can bind two Rab proteins via separate binding sites. Structural analysis allowed us to explain the specificity towards Rab8 family members and the presence of two similar Rab binding sites that must have evolved via gene duplication. This study is the first to thoroughly characterise a Rab effector protein that contains two separate Rab binding sites within a single domain, allowing Micals and EHBPs to bind two Rabs simultaneously, thus suggesting previously unknown functions of these effector molecules in endosomal trafficking.
bMERB domains are bivalent Rab8 family effectors evolved by gene duplication.,Rai A, Oprisko A, Campos J, Fu Y, Friese T, Itzen A, Goody RS, Gazdag EM, Muller MP Elife. 2016 Aug 23;5. pii: e18675. doi: 10.7554/eLife.18675. PMID:27552051[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Babbey CM, Ahktar N, Wang E, Chen CC, Grant BD, Dunn KW. Rab10 regulates membrane transport through early endosomes of polarized Madin-Darby canine kidney cells. Mol Biol Cell. 2006 Jul;17(7):3156-75. Epub 2006 Apr 26. PMID:16641372 doi:http://dx.doi.org/10.1091/mbc.E05-08-0799
- ↑ Hutagalung AH, Novick PJ. Role of Rab GTPases in membrane traffic and cell physiology. Physiol Rev. 2011 Jan;91(1):119-49. doi: 10.1152/physrev.00059.2009. PMID:21248164 doi:http://dx.doi.org/10.1152/physrev.00059.2009
- ↑ English AR, Voeltz GK. Rab10 GTPase regulates ER dynamics and morphology. Nat Cell Biol. 2013 Feb;15(2):169-78. doi: 10.1038/ncb2647. Epub 2012 Dec 23. PMID:23263280 doi:http://dx.doi.org/10.1038/ncb2647
- ↑ Rai A, Oprisko A, Campos J, Fu Y, Friese T, Itzen A, Goody RS, Gazdag EM, Muller MP. bMERB domains are bivalent Rab8 family effectors evolved by gene duplication. Elife. 2016 Aug 23;5. pii: e18675. doi: 10.7554/eLife.18675. PMID:27552051 doi:http://dx.doi.org/10.7554/eLife.18675
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