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| | ==solution NMR structure of EB1 C terminus (191-260)== | | ==solution NMR structure of EB1 C terminus (191-260)== |
| - | <StructureSection load='6evi' size='340' side='right'caption='[[6evi]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='6evi' size='340' side='right'caption='[[6evi]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6evi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EVI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EVI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6evi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EVI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EVI FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Mapre1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=6evi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6evi OCA], [http://pdbe.org/6evi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6evi RCSB], [http://www.ebi.ac.uk/pdbsum/6evi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6evi 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=6evi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6evi OCA], [https://pdbe.org/6evi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6evi RCSB], [https://www.ebi.ac.uk/pdbsum/6evi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6evi ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MARE1_MOUSE MARE1_MOUSE]] Plus-end tracking protein (+TIP) that binds to the plus-end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes cytoplasmic microtubule nucleation and elongation. May be involved in spindle function by stabilizing microtubules and anchoring them at centrosomes. Also acts as a regulator of minus-end microtubule organization: interacts with the complex formed by AKAP9 and PDE4DIP, leading to recruit CAMSAP2 to the Golgi apparatus, thereby tethering non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement. Promotes elongation of CAMSAP2-decorated microtubule stretches on the minus-end of microtubules. Acts as a regulator of autophagosome transport via interaction with CAMSAP2 (By similarity). May play a role in cell migration (PubMed:15311282).[UniProtKB:Q15691]<ref>PMID:15311282</ref> | + | [https://www.uniprot.org/uniprot/MARE1_MOUSE MARE1_MOUSE] Plus-end tracking protein (+TIP) that binds to the plus-end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes cytoplasmic microtubule nucleation and elongation. May be involved in spindle function by stabilizing microtubules and anchoring them at centrosomes. Also acts as a regulator of minus-end microtubule organization: interacts with the complex formed by AKAP9 and PDE4DIP, leading to recruit CAMSAP2 to the Golgi apparatus, thereby tethering non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement. Promotes elongation of CAMSAP2-decorated microtubule stretches on the minus-end of microtubules. Acts as a regulator of autophagosome transport via interaction with CAMSAP2 (By similarity). May play a role in cell migration (PubMed:15311282).[UniProtKB:Q15691]<ref>PMID:15311282</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== |
| - | *[[Microtubule-associated protein|Microtubule-associated protein]] | + | *[[End-binding protein|End-binding protein]] |
| | + | *[[Microtubule-associated protein 3D structures|Microtubule-associated protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Almeida, T B]] | + | [[Category: Almeida TB]] |
| - | [[Category: Barsukov, I L]] | + | [[Category: Barsukov IL]] |
| - | [[Category: Apc-binding protein eb1]]
| + | |
| - | [[Category: Eb1]]
| + | |
| - | [[Category: End-binding protein]]
| + | |
| - | [[Category: Mapre1]]
| + | |
| - | [[Category: Microtubule]]
| + | |
| - | [[Category: Microtubule-associated protein rp/eb family member 1]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Sxip]]
| + | |
| Structural highlights
Function
MARE1_MOUSE Plus-end tracking protein (+TIP) that binds to the plus-end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes cytoplasmic microtubule nucleation and elongation. May be involved in spindle function by stabilizing microtubules and anchoring them at centrosomes. Also acts as a regulator of minus-end microtubule organization: interacts with the complex formed by AKAP9 and PDE4DIP, leading to recruit CAMSAP2 to the Golgi apparatus, thereby tethering non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement. Promotes elongation of CAMSAP2-decorated microtubule stretches on the minus-end of microtubules. Acts as a regulator of autophagosome transport via interaction with CAMSAP2 (By similarity). May play a role in cell migration (PubMed:15311282).[UniProtKB:Q15691][1]
Publication Abstract from PubMed
End binding protein 1 (EB1) is a key element in the complex network of protein-protein interactions at microtubule (MT) growing ends, which has a fundamental role in MT polymerisation. EB1 is an important protein target as it is involved in regulating MT dynamic behaviour, and has been associated with several disease states, such as cancer and neuronal diseases. Diverse EB1 binding partners are recognised through a conserved four amino acid motif, (serine-X-isoleucine-proline) which exists within an intrinsically disordered region. Here we report the use of a multidisciplinary computational and experimental approach for the discovery of the first small molecule scaffold which targets the EB1 recruiting domain. This approach includes virtual screening (structure- and ligand-based design) and multiparameter compound selection. Subsequent studies on the selected compounds enabled the elucidation of the NMR structures of the C-terminal domain of EB1 in the free form and complexed with a small molecule. These structures show that the binding site is not preformed in solution, and ligand binding is fundamental for the binding site formation. This work is a successful demonstration of the combination of modelling and experimental methods to enable the discovery of compounds which bind to these challenging systems.
Targeting SxIP-EB1 interaction: An integrated approach to the discovery of small molecule modulators of dynamic binding sites.,Almeida TB, Carnell AJ, Barsukov IL, Berry NG Sci Rep. 2017 Nov 14;7(1):15533. doi: 10.1038/s41598-017-15502-6. PMID:29138501[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wen Y, Eng CH, Schmoranzer J, Cabrera-Poch N, Morris EJ, Chen M, Wallar BJ, Alberts AS, Gundersen GG. EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration. Nat Cell Biol. 2004 Sep;6(9):820-30. Epub 2004 Aug 15. PMID:15311282 doi:http://dx.doi.org/10.1038/ncb1160
- ↑ Almeida TB, Carnell AJ, Barsukov IL, Berry NG. Targeting SxIP-EB1 interaction: An integrated approach to the discovery of small molecule modulators of dynamic binding sites. Sci Rep. 2017 Nov 14;7(1):15533. doi: 10.1038/s41598-017-15502-6. PMID:29138501 doi:http://dx.doi.org/10.1038/s41598-017-15502-6
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