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| | ==Crystal Structure of Human Rab5A in complex with the C2H2 Zinc Finger of EEA1== | | ==Crystal Structure of Human Rab5A in complex with the C2H2 Zinc Finger of EEA1== |
| - | <StructureSection load='3mjh' size='340' side='right' caption='[[3mjh]], [[Resolution|resolution]] 2.03Å' scene=''> | + | <StructureSection load='3mjh' size='340' side='right'caption='[[3mjh]], [[Resolution|resolution]] 2.03Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3mjh]] 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=3MJH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MJH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3mjh]] 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=3MJH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MJH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAB5, RAB5A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Early Endosomal Antigen1(EEA1), EEA1, ZFYVE2 ([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">RAB5, RAB5A ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Early Endosomal Antigen1(EEA1), EEA1, ZFYVE2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Small_monomeric_GTPase Small monomeric GTPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.5.2 3.6.5.2] </span></td></tr> | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Small_monomeric_GTPase Small monomeric GTPase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.5.2 3.6.5.2] </span></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=3mjh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mjh OCA], [http://pdbe.org/3mjh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3mjh RCSB], [http://www.ebi.ac.uk/pdbsum/3mjh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3mjh 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=3mjh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mjh OCA], [https://pdbe.org/3mjh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mjh RCSB], [https://www.ebi.ac.uk/pdbsum/3mjh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mjh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RAB5A_HUMAN RAB5A_HUMAN]] Required for the fusion of plasma membranes and early endosomes. Contributes to the regulation of filopodia extension.<ref>PMID:14978216</ref> [[http://www.uniprot.org/uniprot/EEA1_HUMAN EEA1_HUMAN]] Binds phospholipid vesicles containing phosphatidylinositol 3-phosphate and participates in endosomal trafficking. | + | [[https://www.uniprot.org/uniprot/RAB5A_HUMAN RAB5A_HUMAN]] Required for the fusion of plasma membranes and early endosomes. Contributes to the regulation of filopodia extension.<ref>PMID:14978216</ref> [[https://www.uniprot.org/uniprot/EEA1_HUMAN EEA1_HUMAN]] Binds phospholipid vesicles containing phosphatidylinositol 3-phosphate and participates in endosomal trafficking. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Small monomeric GTPase]] | | [[Category: Small monomeric GTPase]] |
| | [[Category: Eathiraj, S]] | | [[Category: Eathiraj, S]] |
| Structural highlights
3mjh 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.
| | Ligands: | , , |
| Gene: | RAB5, RAB5A (HUMAN), Early Endosomal Antigen1(EEA1), EEA1, ZFYVE2 (HUMAN) |
| Activity: | Small monomeric GTPase, with EC number 3.6.5.2 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[RAB5A_HUMAN] Required for the fusion of plasma membranes and early endosomes. Contributes to the regulation of filopodia extension.[1] [EEA1_HUMAN] Binds phospholipid vesicles containing phosphatidylinositol 3-phosphate and participates in endosomal trafficking.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Regulation of endosomal trafficking by Rab GTPases depends on selective interactions with multivalent effectors, including EEA1 and Rabenosyn-5, which facilitate endosome tethering, sorting, and fusion. Both EEA1 and Rabenosyn-5 contain a distinctive N-terminal C(2)H(2) zinc finger that binds Rab5. How these C(2)H(2) zinc fingers recognize Rab GTPases remains unknown. Here, we report the crystal structure of Rab5A in complex with the EEA1 C(2)H(2) zinc finger. The binding interface involves all elements of the zinc finger as well as a short N-terminal extension but is restricted to the switch and interswitch regions of Rab5. High selectivity for Rab5 and, to a lesser extent Rab22, is observed in quantitative profiles of binding to Rab family GTPases. Although critical determinants are identified in both switch regions, Rab4-to-Rab5 conversion-of-specificity mutants reveal an essential requirement for additional substitutions in the proximal protein core that are predicted to indirectly influence recognition through affects on the structure and conformational stability of the switch regions.
Structural basis for Rab GTPase recognition and endosome tethering by the C2H2 zinc finger of Early Endosomal Autoantigen 1 (EEA1).,Mishra A, Eathiraj S, Corvera S, Lambright DG Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10866-71. Epub 2010 Jun 1. PMID:20534488[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gauthier-Campbell C, Bredt DS, Murphy TH, El-Husseini Ael-D. Regulation of dendritic branching and filopodia formation in hippocampal neurons by specific acylated protein motifs. Mol Biol Cell. 2004 May;15(5):2205-17. Epub 2004 Feb 20. PMID:14978216 doi:10.1091/mbc.E03-07-0493
- ↑ Mishra A, Eathiraj S, Corvera S, Lambright DG. Structural basis for Rab GTPase recognition and endosome tethering by the C2H2 zinc finger of Early Endosomal Autoantigen 1 (EEA1). Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10866-71. Epub 2010 Jun 1. PMID:20534488
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