2v8f: Difference between revisions

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==Overview==

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.

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.

==About this Structure==

2V8F is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=GOL:'>GOL</scene> and <scene name='pdbligand=IPA:'>IPA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=AC1:So4 Binding Site For Chain A'>AC1</scene>, <scene name='pdbsite=AC2:So4 Binding Site For Chain B'>AC2</scene>, <scene name='pdbsite=AC3:Gol Binding Site For Chain B'>AC3</scene>, <scene name='pdbsite=AC4:Ipa Binding Site For Chain B'>AC4</scene>, <scene name='pdbsite=AC5:Na Binding Site For Chain A'>AC5</scene>, <scene name='pdbsite=AC6:So4 Binding Site For Chain A'>AC6</scene>, <scene name='pdbsite=AC7:So4 Binding Site For Chain B'>AC7</scene> and <scene name='pdbsite=AC8:So4 Binding Site For Chain B'>AC8</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V8F OCA].

2V8F is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=GOL:'>GOL</scene> and <scene name='pdbligand=IPA:'>IPA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:So4+Binding+Site+For+Chain+B'>AC2</scene>, <scene name='pdbsite=AC3:Gol+Binding+Site+For+Chain+B'>AC3</scene>, <scene name='pdbsite=AC4:Ipa+Binding+Site+For+Chain+B'>AC4</scene>, <scene name='pdbsite=AC5:Na+Binding+Site+For+Chain+A'>AC5</scene>, <scene name='pdbsite=AC6:So4+Binding+Site+For+Chain+A'>AC6</scene>, <scene name='pdbsite=AC7:So4+Binding+Site+For+Chain+B'>AC7</scene> and <scene name='pdbsite=AC8:So4+Binding+Site+For+Chain+B'>AC8</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V8F OCA].

==Reference==

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[[Category: protein-binding]]

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@@ Line 4: / Line 4: @@
 ==Overview==
-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.
+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.
 ==About this Structure==
-V8F is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=GOL:'>GOL</scene> and <scene name='pdbligand=IPA:'>IPA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=AC1:So4 Binding Site For Chain A'>AC1</scene>, <scene name='pdbsite=AC2:So4 Binding Site For Chain B'>AC2</scene>, <scene name='pdbsite=AC3:Gol Binding Site For Chain B'>AC3</scene>, <scene name='pdbsite=AC4:Ipa Binding Site For Chain B'>AC4</scene>, <scene name='pdbsite=AC5:Na Binding Site For Chain A'>AC5</scene>, <scene name='pdbsite=AC6:So4 Binding Site For Chain A'>AC6</scene>, <scene name='pdbsite=AC7:So4 Binding Site For Chain B'>AC7</scene> and <scene name='pdbsite=AC8:So4 Binding Site For Chain B'>AC8</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V8F OCA].
+V8F is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=GOL:'>GOL</scene> and <scene name='pdbligand=IPA:'>IPA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:So4+Binding+Site+For+Chain+B'>AC2</scene>, <scene name='pdbsite=AC3:Gol+Binding+Site+For+Chain+B'>AC3</scene>, <scene name='pdbsite=AC4:Ipa+Binding+Site+For+Chain+B'>AC4</scene>, <scene name='pdbsite=AC5:Na+Binding+Site+For+Chain+A'>AC5</scene>, <scene name='pdbsite=AC6:So4+Binding+Site+For+Chain+A'>AC6</scene>, <scene name='pdbsite=AC7:So4+Binding+Site+For+Chain+B'>AC7</scene> and <scene name='pdbsite=AC8:So4+Binding+Site+For+Chain+B'>AC8</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V8F OCA].
 ==Reference==
@@ Line 29: / Line 29: @@
 [[Category: protein-binding]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:36:05 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:54:08 2008''