|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6djl' size='340' side='right'caption='[[6djl]], [[Resolution|resolution]] 3.10Å' scene=''> | | <StructureSection load='6djl' size='340' side='right'caption='[[6djl]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6djl]] is a 8 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=6DJL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DJL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6djl]] is a 8 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=6DJL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DJL FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAB11A, RAB11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SH3BP5, SAB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 3.1000116Å</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=6djl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6djl OCA], [http://pdbe.org/6djl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6djl RCSB], [http://www.ebi.ac.uk/pdbsum/6djl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6djl 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=6djl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6djl OCA], [https://pdbe.org/6djl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6djl RCSB], [https://www.ebi.ac.uk/pdbsum/6djl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6djl 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/3BP5_HUMAN 3BP5_HUMAN]] Inhibits the auto- and transphosphorylation activity of BTK. Plays a negative regulatory role in BTK-related cytoplasmic signaling in B-cells. May be involved in BCR-induced apoptotic cell death.<ref>PMID:10339589</ref> <ref>PMID:9571151</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 ==
| + | |
| - | The GTPase Rab11 plays key roles in receptor recycling, oogenesis, autophagosome formation, and ciliogenesis. However, investigating Rab11 regulation has been hindered by limited molecular detail describing activation by cognate guanine nucleotide exchange factors (GEFs). Here, we present the structure of Rab11 bound to the GEF SH3BP5, along with detailed characterization of Rab-GEF specificity. The structure of SH3BP5 shows a coiled-coil architecture that mediates exchange through a unique Rab-GEF interaction. Furthermore, it reveals a rearrangement of the switch I region of Rab11 compared with solved Rab-GEF structures, with a constrained conformation when bound to SH3BP5. Mutation of switch I provides insights into the molecular determinants that allow for Rab11 selectivity over evolutionarily similar Rab GTPases present on Rab11-positive organelles. Moreover, we show that GEF-deficient mutants of SH3BP5 show greatly decreased Rab11 activation in cellular assays of active Rab11. Overall, our results give molecular insight into Rab11 regulation, and how Rab-GEF specificity is achieved.
| + | |
| - | | + | |
| - | Structural determinants of Rab11 activation by the guanine nucleotide exchange factor SH3BP5.,Jenkins ML, Margaria JP, Stariha JTB, Hoffmann RM, McPhail JA, Hamelin DJ, Boulanger MJ, Hirsch E, Burke JE Nat Commun. 2018 Sep 14;9(1):3772. doi: 10.1038/s41467-018-06196-z. PMID:30217979<ref>PMID:30217979</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6djl" 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: Boulanger, M J]] | + | [[Category: Boulanger MJ]] |
| - | [[Category: Burke, J E]] | + | [[Category: Burke JE]] |
| - | [[Category: Jenkins, M L]] | + | [[Category: Jenkins ML]] |
| - | [[Category: Guanine nucleotide exchange factor]]
| + | |
| - | [[Category: Membrane trafficking]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| - | [[Category: Rab gtpase]]
| + | |
| - | [[Category: Signaling protein-protein transport complex]]
| + | |
| 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
|
