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| | ==GEF domain of DENND 1B in complex with Rab GTPase Rab35== | | ==GEF domain of DENND 1B in complex with Rab GTPase Rab35== |
| - | <StructureSection load='3tw8' size='340' side='right' caption='[[3tw8]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='3tw8' size='340' side='right'caption='[[3tw8]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3tw8]] is a 4 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=3TW8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TW8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3tw8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TW8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TW8 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2fol|2fol]], [[1yzn|1yzn]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2fol|2fol]], [[1yzn|1yzn]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DENND1B, C1orf218, FAM31B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RAB35, RAB1C, RAY ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DENND1B, C1orf218, FAM31B ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RAB35, RAB1C, RAY ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3tw8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tw8 OCA], [http://pdbe.org/3tw8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tw8 RCSB], [http://www.ebi.ac.uk/pdbsum/3tw8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tw8 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=3tw8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tw8 OCA], [https://pdbe.org/3tw8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tw8 RCSB], [https://www.ebi.ac.uk/pdbsum/3tw8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tw8 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DEN1B_HUMAN DEN1B_HUMAN]] Guanine nucleotide exchange factor (GEF) for RAB35. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form. May play a role in clathrin-mediated endocytosis.<ref>PMID:20154091</ref> <ref>PMID:20937701</ref> [[http://www.uniprot.org/uniprot/RAB35_HUMAN RAB35_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 sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in the process of endocytosis and is an essential rate-limiting regulator of the fast recycling pathway back to the plasma membrane. During cytokinesis, required for the postfurrowing terminal steps, namely for intercellular bridge stability and abscission, possibly by controlling phosphatidylinositol 4,5-bis phosphate (PIP2) and SEPT2 localization at the intercellular bridge. May indirectly regulate neurite outgrowth.<ref>PMID:16950109</ref> <ref>PMID:21951725</ref> | + | [[https://www.uniprot.org/uniprot/DEN1B_HUMAN DEN1B_HUMAN]] Guanine nucleotide exchange factor (GEF) for RAB35. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form. May play a role in clathrin-mediated endocytosis.<ref>PMID:20154091</ref> <ref>PMID:20937701</ref> [[https://www.uniprot.org/uniprot/RAB35_HUMAN RAB35_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 sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in the process of endocytosis and is an essential rate-limiting regulator of the fast recycling pathway back to the plasma membrane. During cytokinesis, required for the postfurrowing terminal steps, namely for intercellular bridge stability and abscission, possibly by controlling phosphatidylinositol 4,5-bis phosphate (PIP2) and SEPT2 localization at the intercellular bridge. May indirectly regulate neurite outgrowth.<ref>PMID:16950109</ref> <ref>PMID:21951725</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[GTP-binding protein|GTP-binding protein]] | + | *[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] |
| | + | *[[Ras-related protein Rab 3D structures|Ras-related protein Rab 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Kummel, D]] | | [[Category: Kummel, D]] |
| | [[Category: Reinisch, K M]] | | [[Category: Reinisch, K M]] |
| Structural highlights
3tw8 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | |
| Gene: | DENND1B, C1orf218, FAM31B (HUMAN), RAB35, RAB1C, RAY (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[DEN1B_HUMAN] Guanine nucleotide exchange factor (GEF) for RAB35. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form. May play a role in clathrin-mediated endocytosis.[1] [2] [RAB35_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 sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in the process of endocytosis and is an essential rate-limiting regulator of the fast recycling pathway back to the plasma membrane. During cytokinesis, required for the postfurrowing terminal steps, namely for intercellular bridge stability and abscission, possibly by controlling phosphatidylinositol 4,5-bis phosphate (PIP2) and SEPT2 localization at the intercellular bridge. May indirectly regulate neurite outgrowth.[3] [4]
Publication Abstract from PubMed
Rab GTPases are key regulators of membrane traffic pathways within eukaryotic cells. They are specifically activated by guanine nucleotide exchange factors (GEFs), which convert them from their "inactive" GDP-bound form to the "active" GTP-bound form. In higher eukaryotes, proteins containing DENN-domains comprise a major GEF family. Here we describe at 2.1-A resolution the first structure of a DENN-domain protein, DENND1B-S, complexed with its substrate Rab35, providing novel insights as to how DENN-domain GEFs interact with and activate Rabs. DENND1B-S is bi-lobed, and interactions with Rab35 are through conserved surfaces in both lobes. Rab35 binds via switch regions I and II, around the nucleotide-binding pocket. Positional shifts in Rab residues required for nucleotide binding may lower its affinity for bound GDP, and a conformational change in switch I, which makes the nucleotide-binding pocket more solvent accessible, likely also facilitates exchange.
Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate.,Wu X, Bradley MJ, Cai Y, Kummel D, De La Cruz EM, Barr FA, Reinisch KM Proc Natl Acad Sci U S A. 2011 Nov 7. PMID:22065758[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Marat AL, McPherson PS. The connecdenn family, Rab35 guanine nucleotide exchange factors interfacing with the clathrin machinery. J Biol Chem. 2010 Apr 2;285(14):10627-37. doi: 10.1074/jbc.M109.050930. Epub 2010, Feb 12. PMID:20154091 doi:http://dx.doi.org/10.1074/jbc.M109.050930
- ↑ Yoshimura S, Gerondopoulos A, Linford A, Rigden DJ, Barr FA. Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors. J Cell Biol. 2010 Oct 18;191(2):367-81. doi: 10.1083/jcb.201008051. Epub 2010 Oct, 11. PMID:20937701 doi:http://dx.doi.org/10.1083/jcb.201008051
- ↑ Kouranti I, Sachse M, Arouche N, Goud B, Echard A. Rab35 regulates an endocytic recycling pathway essential for the terminal steps of cytokinesis. Curr Biol. 2006 Sep 5;16(17):1719-25. PMID:16950109 doi:http://dx.doi.org/10.1016/j.cub.2006.07.020
- ↑ Rahajeng J, Giridharan SS, Cai B, Naslavsky N, Caplan S. MICAL-L1 is a tubular endosomal membrane hub that connects Rab35 and Arf6 with Rab8a. Traffic. 2012 Jan;13(1):82-93. doi: 10.1111/j.1600-0854.2011.01294.x. Epub 2011, Oct 24. PMID:21951725 doi:http://dx.doi.org/10.1111/j.1600-0854.2011.01294.x
- ↑ Wu X, Bradley MJ, Cai Y, Kummel D, De La Cruz EM, Barr FA, Reinisch KM. Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate. Proc Natl Acad Sci U S A. 2011 Nov 7. PMID:22065758 doi:10.1073/pnas.1110415108
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