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| | ==Mouse Profilin IIa in complex with the proline-rich domain of VASP== | | ==Mouse Profilin IIa in complex with the proline-rich domain of VASP== |
| - | <StructureSection load='2v8c' size='340' side='right' caption='[[2v8c]], [[Resolution|resolution]] 1.98Å' scene=''> | + | <StructureSection load='2v8c' size='340' side='right'caption='[[2v8c]], [[Resolution|resolution]] 1.98Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2v8c]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V8C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2V8C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2v8c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V8C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V8C FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 1.98Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2v8f|2v8f]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2v8c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v8c OCA], [http://pdbe.org/2v8c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2v8c RCSB], [http://www.ebi.ac.uk/pdbsum/2v8c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2v8c 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=2v8c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v8c OCA], [https://pdbe.org/2v8c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v8c RCSB], [https://www.ebi.ac.uk/pdbsum/2v8c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v8c ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PROF2_MOUSE PROF2_MOUSE]] Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. [[http://www.uniprot.org/uniprot/VASP_MOUSE VASP_MOUSE]] Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance, lamellipodial and filopodial dynamics, platelet activation and cell migration. VASP promotes actin filament elongation. It protects the barbed end of growing actin filaments against capping and increases the rate of actin polymerization in the presence of capping protein. VASP stimulates actin filament elongation by promoting the transfer of profilin-bound actin monomers onto the barbed end of growing actin filaments. Plays a role in actin-based mobility of Listeria monocytogenes in host cells. Regulates actin dynamics in platelets and plays an important role in regulating platelet aggregation (By similarity).<ref>PMID:10660044</ref> | + | [https://www.uniprot.org/uniprot/PROF2_MOUSE PROF2_MOUSE] Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Profilin|Profilin]] | + | *[[Profilin 3D Structures|Profilin 3D Structures]] |
| | + | *[[Vasodilator-stimulated phosphoprotein|Vasodilator-stimulated phosphoprotein]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Downer, J]] | + | [[Category: Mus musculus]] |
| - | [[Category: Kursula, P]] | + | [[Category: Downer J]] |
| - | [[Category: Wilmanns, M]] | + | [[Category: Kursula P]] |
| - | [[Category: Witke, W]] | + | [[Category: Wilmanns M]] |
| - | [[Category: Acetylation]]
| + | [[Category: Witke W]] |
| - | [[Category: Actin-binding]]
| + | |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Cytoskeleton]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Protein-binding]]
| + | |
| Structural highlights
Function
PROF2_MOUSE Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG.
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
Profilins are small proteins capable of binding actin, poly-l-proline and other proline-rich sequences, and phosphatidylinositol (4,5)-bisphosphate. A number of proline-rich ligands for profilin have been characterised, including proteins of the Ena/VASP and formin families. We have determined the high-resolution crystal structures of mouse profilin 2a in complex with peptides from two functionally important ligands from different families, VASP and mDia1. The structures show that the binding mode of the peptide ligand is strongly affected by the non-proline residues in the sequence, and the peptides from VASP and mDia1 bind to profilin 2a in distinct modes. The high resolution of the crystallographic data allowed us to detect conserved CH-pi hydrogen bonds between the peptide and profilin in both complexes. Furthermore, both peptides, which are shown to have micromolar affinity, induced the dimerisation of profilin, potentially leading to functionally different ligand-profilin-actin complexes. The peptides did not significantly affect actin polymerisation kinetics in the presence or in the absence of profilin 2a. Mutant profilins were tested for binding to poly-L-proline and the VASP and mDia1 peptides, and the F139A mutant bound proline-rich ligands with near-native affinity. Peptide blotting using a series of designed peptides with profilins 1 and 2a indicates differences between the two profilins towards proline-rich peptides from mDia1 and VASP. Our data provide structural insights into the mechanisms of mDia1 and VASP regulated actin polymerisation.
High-resolution structural analysis of mammalian profilin 2a complex formation with two physiological ligands: the formin homology 1 domain of mDia1 and the proline-rich domain of VASP.,Kursula P, Kursula I, Massimi M, Song YH, Downer J, Stanley WA, Witke W, Wilmanns M J Mol Biol. 2008 Jan 4;375(1):270-90. Epub 2007 Oct 24. PMID:18001770[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kursula P, Kursula I, Massimi M, Song YH, Downer J, Stanley WA, Witke W, Wilmanns M. High-resolution structural analysis of mammalian profilin 2a complex formation with two physiological ligands: the formin homology 1 domain of mDia1 and the proline-rich domain of VASP. J Mol Biol. 2008 Jan 4;375(1):270-90. Epub 2007 Oct 24. PMID:18001770 doi:10.1016/j.jmb.2007.10.050
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