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| | <StructureSection load='4c4p' size='340' side='right'caption='[[4c4p]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='4c4p' size='340' side='right'caption='[[4c4p]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4c4p]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C4P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C4P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4c4p]] is a 2 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=4C4P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C4P 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='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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4c4p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c4p OCA], [http://pdbe.org/4c4p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4c4p RCSB], [http://www.ebi.ac.uk/pdbsum/4c4p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4c4p 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=4c4p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c4p OCA], [https://pdbe.org/4c4p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c4p RCSB], [https://www.ebi.ac.uk/pdbsum/4c4p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c4p ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RB11A_HUMAN RB11A_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. That Rab regulates endocytic recycling. Acts as a major regulator of membrane delivery during cytokinesis. Together with MYO5B and RAB8A participates in epithelial cell polarization. Together with RAB3IP, RAB8A, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis. Together with MYO5B participates in CFTR trafficking to the plasma membrane and TF (Transferrin) recycling in nonpolarized cells. Required in a complex with MYO5B and RAB11FIP2 for the transport of NPC1L1 to the plasma membrane. Participates in the sorting and basolateral transport of CDH1 from the Golgi apparatus to the plasma membrane. Regulates the recycling of FCGRT (receptor of Fc region of monomeric Ig G) to basolateral membranes. May also play a role in melanosome transport and release from melanocytes.<ref>PMID:15601896</ref> <ref>PMID:15689490</ref> <ref>PMID:17462998</ref> <ref>PMID:19542231</ref> <ref>PMID:20890297</ref> <ref>PMID:21282656</ref> [[http://www.uniprot.org/uniprot/RFIP2_HUMAN RFIP2_HUMAN]] A Rab11 effector protein acting in the regulation of the transport of vesicles from the endosomal recycling compartment (ERC) to the plasma membrane. Also involved in receptor-mediated endocytosis and membrane trafficking of recycling endosomes, probably originating from clathrin-coated vesicles. Binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and phosphatidic acid (PA). Required in a complex with MYO5B and RAB11 for the transport of NPC1L1 to the plasma membrane. Also acts as a regulator of cell polarity.<ref>PMID:12364336</ref> <ref>PMID:15304524</ref> <ref>PMID:16775013</ref> <ref>PMID:19542231</ref> | + | [[https://www.uniprot.org/uniprot/RB11A_HUMAN RB11A_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. That Rab regulates endocytic recycling. Acts as a major regulator of membrane delivery during cytokinesis. Together with MYO5B and RAB8A participates in epithelial cell polarization. Together with RAB3IP, RAB8A, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis. Together with MYO5B participates in CFTR trafficking to the plasma membrane and TF (Transferrin) recycling in nonpolarized cells. Required in a complex with MYO5B and RAB11FIP2 for the transport of NPC1L1 to the plasma membrane. Participates in the sorting and basolateral transport of CDH1 from the Golgi apparatus to the plasma membrane. Regulates the recycling of FCGRT (receptor of Fc region of monomeric Ig G) to basolateral membranes. May also play a role in melanosome transport and release from melanocytes.<ref>PMID:15601896</ref> <ref>PMID:15689490</ref> <ref>PMID:17462998</ref> <ref>PMID:19542231</ref> <ref>PMID:20890297</ref> <ref>PMID:21282656</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Rab small GTPases are the master regulators of intracellular trafficking in eukaryotes. They mediate spatial and temporal recruitment of effector proteins to distinct cellular compartments through GTP-induced changes in their conformation. Despite numerous structural studies, the molecular basis for Rab/effector specificity and subsequent biological activity remains poorly understood. Rab25, also known as Rab11c, which is epithelial-specific, has been heavily implicated in ovarian cancer development and independently appears to act as a tumour suppressor in the context of a distinct subset of carcinomas. Here, we show that Rab25 associates with FIP2 and can recruit this effector protein to endosomal membranes. We report the crystal structure of Rab25 in complex with the C-terminal region of FIP2, which consists of a central dimeric FIP2 coiled-coil that mediates a heterotetrameric Rab25-(FIP2)2-Rab25 complex. Thermodynamic analyses show that, despite a relatively conserved interface, FIP2 binds to Rab25 with an approximate 3-fold weaker affinity than to Rab11a. Reduced affinity is mainly associated with lower enthalpic gains for Rab25:FIP2 complex formation, and can be attributed to subtle differences in the conformations of switch 1 and switch 2. These cellular, structural and thermodynamic studies provide insight into the Rab11/Rab25 subfamily of small GTPases that regulate endosomal trafficking pathways in eukaryotes.
| + | |
| - | | + | |
| - | Structural and functional analysis of FIP2 binding to the endosome-localised Rab25 GTPase.,Lall P, Horgan CP, Oda S, Franklin E, Sultana A, Hanscom SR, McCaffrey MW, Khan AR Biochim Biophys Acta. 2013 Sep 19. pii: S1570-9639(13)00317-8. doi:, 10.1016/j.bbapap.2013.09.005. PMID:24056041<ref>PMID:24056041</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4c4p" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Ras-related protein Rab|Ras-related protein Rab]] | + | *[[Ras-related protein Rab 3D structures|Ras-related protein Rab 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Khan, A R]] | + | [[Category: Khan AR]] |
| - | [[Category: Sultana, A]] | + | [[Category: Sultana A]] |
| - | [[Category: Effector]]
| + | |
| - | [[Category: Endosome]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| - | [[Category: Vesicle trafficking]]
| + | |
| Structural highlights
Function
[RB11A_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. That Rab regulates endocytic recycling. Acts as a major regulator of membrane delivery during cytokinesis. Together with MYO5B and RAB8A participates in epithelial cell polarization. Together with RAB3IP, RAB8A, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis. Together with MYO5B participates in CFTR trafficking to the plasma membrane and TF (Transferrin) recycling in nonpolarized cells. Required in a complex with MYO5B and RAB11FIP2 for the transport of NPC1L1 to the plasma membrane. Participates in the sorting and basolateral transport of CDH1 from the Golgi apparatus to the plasma membrane. Regulates the recycling of FCGRT (receptor of Fc region of monomeric Ig G) to basolateral membranes. May also play a role in melanosome transport and release from melanocytes.[1] [2] [3] [4] [5] [6]
See Also
References
- ↑ Wilson GM, Fielding AB, Simon GC, Yu X, Andrews PD, Hames RS, Frey AM, Peden AA, Gould GW, Prekeris R. The FIP3-Rab11 protein complex regulates recycling endosome targeting to the cleavage furrow during late cytokinesis. Mol Biol Cell. 2005 Feb;16(2):849-60. Epub 2004 Dec 15. PMID:15601896 doi:10.1091/mbc.E04-10-0927
- ↑ Lock JG, Stow JL. Rab11 in recycling endosomes regulates the sorting and basolateral transport of E-cadherin. Mol Biol Cell. 2005 Apr;16(4):1744-55. Epub 2005 Feb 2. PMID:15689490 doi:10.1091/mbc.E04-10-0867
- ↑ Swiatecka-Urban A, Talebian L, Kanno E, Moreau-Marquis S, Coutermarsh B, Hansen K, Karlson KH, Barnaby R, Cheney RE, Langford GM, Fukuda M, Stanton BA. Myosin Vb is required for trafficking of the cystic fibrosis transmembrane conductance regulator in Rab11a-specific apical recycling endosomes in polarized human airway epithelial cells. J Biol Chem. 2007 Aug 10;282(32):23725-36. Epub 2007 Apr 26. PMID:17462998 doi:10.1074/jbc.M608531200
- ↑ Chu BB, Ge L, Xie C, Zhao Y, Miao HH, Wang J, Li BL, Song BL. Requirement of myosin Vb.Rab11a.Rab11-FIP2 complex in cholesterol-regulated translocation of NPC1L1 to the cell surface. J Biol Chem. 2009 Aug 14;284(33):22481-90. doi: 10.1074/jbc.M109.034355. Epub, 2009 Jun 19. PMID:19542231 doi:10.1074/jbc.M109.034355
- ↑ Bryant DM, Datta A, Rodriguez-Fraticelli AE, Peranen J, Martin-Belmonte F, Mostov KE. A molecular network for de novo generation of the apical surface and lumen. Nat Cell Biol. 2010 Nov;12(11):1035-45. doi: 10.1038/ncb2106. Epub 2010 Oct 3. PMID:20890297 doi:10.1038/ncb2106
- ↑ Roland JT, Bryant DM, Datta A, Itzen A, Mostov KE, Goldenring JR. Rab GTPase-Myo5B complexes control membrane recycling and epithelial polarization. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2789-94. doi:, 10.1073/pnas.1010754108. Epub 2011 Jan 31. PMID:21282656 doi:10.1073/pnas.1010754108
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