Parvin: Difference between revisions

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Alpha-parvin's structure can be divided into four regions: 1) N-terminal flexible domain (residues 1-96), 2) N-terminal CH domain (97-200 according to SMART<ref>PMID: 9600884</ref>), 3) linker region (201-241) and 4) C-terminal CH domain (242-372 identified by limited subtilisin proteolysis<ref>PMID: 18940607</ref>). Most interactions of alpha-parvin are mapped to the C-terminal CH domain, but CdGAP and perhaps alphaPIX or other, yet unknown partners, interact with the N-terminal flexibile domain. This flexible domain seems to lack a well defined 3D structure and can therefore be classified as a putative [[Intrinsically Disordered Protein|intrinsically disordered]] region. The interactions of this regions with the binding partners are therefore likely to be characterized by relatively low affinity, but high affinity nonetheless.<ref>PMID: 19265676</ref> The abovementioned phosphorylation sites (serines 4 and 8) involved in focal adhesion regulation are located in this segment, which makes them so called disorder-enhanced phosphorylation sites.<ref>PMID: 14960716</ref><ref>PMID: 18388127</ref>

===C-terminal CH domain===

The calponin-homology (CH) domains are helical structural units around 100 amino acids long. They comprise at least four helices, three of them forming a helical bundle. CH domains usually comprise elements of big multidomain proteins and are present either in singlet<ref>PMID: 19459066</ref> or duplex/tandem arrangement.<ref>PMID: 19565353</ref> The tandem arrangement of CH domains is often associated with F-actin binding<ref>PMID: 9708889</ref><ref>PMID: 18952167</ref> (and is thus called actin-binding domain or ABD), but generally CH domains seem to be characterized by functional plasticity and ability to bind various structural motifs.<ref>PMID: 11911887</ref> In the case of alpha-parvin, the interactions of CH domains with both F-actin and other partners (paxillin, ILK) are observed. The interactions with paxillin and ILK are mediated by a single CH domain, the C-terminal one. This domain has attracted most attention. While no full-length structure of alpha-parvin has been solved to date, the structure of the C-terminal CH domain, on its own<ref>PMID: 18940607</ref> and in complexes (with paxillin<ref>PMID: 18940607</ref><ref>PMID: 18508764</ref> and the pseudokinase domain of ILK<ref>PMID: 20005845</ref>) are available.

[[Image:Consurf_key_small.gif|right|200px]]The scene on the left shows the structure of the <scene name='~~User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin/~~/Parvin/1'>C-terminal CH domain of alpha-parvin</scene> at around 1.05 Å ([[2vzc]]). When a sequence alignment of alpha-parvin with all its sequence homologues is performed and the protein is coloured according to <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin/3'>the degree of sequence conservation</scene>, one can see that the highest degree of conservation is exhibited by the residues located in <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin/5'>the core helices</scene>, while the residues in linker helices and loops are less conserved. When the <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin_overlap/1'>structural superposition</scene> of the C-terminal CH domain of alpha-parvin and one of the CH domains of alpha-actinin 3 ([[1wku]]) is performed, a good overall overlap is observed, as represented by the RMSD of 1.19 Å for 103 equivalent Cα positions, despite low sequence homology (≤26% identity).<ref>PMID: 18940607</ref> Again the best overlap is seen for the core helices. This suggests that the structural framework of CH domain and its core in particular are quite robust under evolution.

[[Image:Consurf_key_small.gif|right|200px]]The scene on the left shows the structure of the <scene name='Alpha-parvin/Parvin/9'>C-terminal CH domain of alpha-parvin</scene> at around 1.05 Å ([[2vzc]]). When a sequence alignment of alpha-parvin with all its sequence homologues is performed and the protein is coloured according to <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin/3'>the degree of sequence conservation</scene>, one can see that the highest degree of conservation is exhibited by the residues located in <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin/5'>the core helices</scene>, while the residues in linker helices and loops are less conserved. When the <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin_overlap/1'>structural superposition</scene> of the C-terminal CH domain of alpha-parvin and one of the CH domains of alpha-actinin 3 ([[1wku]]) is performed, a good overall overlap is observed, as represented by the RMSD of 1.19 Å for 103 equivalent Cα positions, despite low sequence homology (≤26% identity).<ref>PMID: 18940607</ref> Again the best overlap is seen for the core helices. This suggests that the structural framework of CH domain and its core in particular are quite robust under evolution.

The most diverged fragments in the C-terminal CH domain of alpha-parvin correspond to 1) an <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin_overlap/3'>additional helix</scene> (so called N-terminal linker helix; it is labelled αN ~~in the picture above on the right~~) located at the N-terminal end of the domain and not observed in any other CH domain and 2) a <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin_overlap/5'>long loop</scene> between two helices (~~which are labelled~~ αC and αE ~~in the picture above on the right~~). One could ask whether the N-terminal linker helix is an integral part of the C-terminal CH domain or just a part of a linker region between the two CH domains. The fact that it interacts strongly with the core helices by means of both electrostatic (<scene name='Alpha-parvin/Parvin_overlap/1'>residues D248, D251 and D255 with K355 and R359</scene>) and hydrophobic (<scene name='Alpha-parvin/Parvin_overlap/4'>residues F250, L253 and F254 with L354, K355, L358, R359, K260 and L261</scene>) interactions suggests that it is indeed integral to the domain. The long loop mentioned above contains a <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin_overlap/6'>3-amino acid insertion</scene> (313-315) relative to other known CH domains and differs in conformation between different structures of alpha-parvin, suggesting it is relatively flexible.<ref>PMID: 18940607</ref> Interestingly, these two regions, the N-terminal linker helix and the long loop, are involved in binding of alpha-parvin to its binding partners, paxillin and ILK respectively.

The most diverged fragments in the C-terminal CH domain of alpha-parvin correspond to 1) an <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin_overlap/3'>additional helix</scene> (so called N-terminal linker helix; it is labelled αN or helix N) located at the N-terminal end of the domain and not observed in any other CH domain and 2) a <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin_overlap/5'>long loop</scene> between two helices (αC and αE). One could ask whether the N-terminal linker helix is an integral part of the C-terminal CH domain or just a part of a linker region between the two CH domains. The fact that it interacts strongly with the core helices by means of both electrostatic (<scene name='Alpha-parvin/Parvin_overlap/1'>residues D248, D251 and D255 with K355 and R359</scene>) and hydrophobic (<scene name='Alpha-parvin/Parvin_overlap/4'>residues F250, L253 and F254 with L354, K355, L358, R359, K260 and L261</scene>) interactions suggests that it is indeed integral to the domain. The long loop mentioned above contains a <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin_overlap/6'>3-amino acid insertion</scene> (313-315) relative to other known CH domains and differs in conformation between different structures of alpha-parvin, suggesting it is relatively flexible.<ref>PMID: 18940607</ref> Interestingly, these two regions, the N-terminal linker helix and the long loop, are involved in binding of alpha-parvin to its binding partners, paxillin and ILK respectively.

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@@ Line 18: / Line 18: @@
 Alpha-parvin's structure can be divided into four regions: 1) N-terminal flexible domain (residues 1-96), 2) N-terminal CH domain (97-200 according to SMART<ref>PMID: 9600884</ref>), 3) linker region (201-241) and 4) C-terminal CH domain (242-372 identified by limited subtilisin proteolysis<ref>PMID: 18940607</ref>). Most interactions of alpha-parvin are mapped to the C-terminal CH domain, but CdGAP and perhaps alphaPIX or other, yet unknown partners, interact with the N-terminal flexibile domain. This flexible domain seems to lack a well defined 3D structure and can therefore be classified as a putative [[Intrinsically Disordered Protein|intrinsically disordered]] region. The interactions of this regions with the binding partners are therefore likely to be characterized by relatively low affinity, but high affinity nonetheless.<ref>PMID: 19265676</ref> The abovementioned phosphorylation sites (serines 4 and 8) involved in focal adhesion regulation are located in this segment, which makes them so called disorder-enhanced phosphorylation sites.<ref>PMID: 14960716</ref><ref>PMID: 18388127</ref>
-<Structure load='2vzc' scene='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin/1' size='340' frame='true' align='left' caption='Structure of the C-terminal CH domain([[2vzc]])'/>
+<Structure load='2vzc' scene='Alpha-parvin/Parvin/9' size='340' frame='true' align='left' caption='Structure of the C-terminal CH domain([[2vzc]])'/>
 ===C-terminal CH domain===
 The calponin-homology (CH) domains are helical structural units around 100 amino acids long. They comprise at least four helices, three of them forming a helical bundle. CH domains usually comprise elements of big multidomain proteins and are present either in singlet<ref>PMID: 19459066</ref> or duplex/tandem arrangement.<ref>PMID: 19565353</ref> The tandem arrangement of CH domains is often associated with F-actin binding<ref>PMID: 9708889</ref><ref>PMID: 18952167</ref> (and is thus called actin-binding domain or ABD), but generally CH domains seem to be characterized by functional plasticity and ability to bind various structural motifs.<ref>PMID: 11911887</ref> In the case of alpha-parvin, the interactions of CH domains with both F-actin and other partners (paxillin, ILK) are observed. The interactions with paxillin and ILK are mediated by a single CH domain, the C-terminal one. This domain has attracted most attention. While no full-length structure of alpha-parvin has been solved to date, the structure of the C-terminal CH domain, on its own<ref>PMID: 18940607</ref> and in complexes (with paxillin<ref>PMID: 18940607</ref><ref>PMID: 18508764</ref> and the pseudokinase domain of ILK<ref>PMID: 20005845</ref>) are available.
-[[Image:Consurf_key_small.gif|right|200px]]The scene on the left shows the structure of the <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin/1'>C-terminal CH domain of alpha-parvin</scene> at around 1.05 Å ([[2vzc]]). When a sequence alignment of alpha-parvin with all its sequence homologues is performed and the protein is coloured according to <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin/3'>the degree of sequence conservation</scene>, one can see that the highest degree of conservation is exhibited by the residues located in <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin/5'>the core helices</scene>, while the residues in linker helices and loops are less conserved. When the <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin_overlap/1'>structural superposition</scene> of the <font color='brown'>C-terminal CH domain of alpha-parvin</font> and <font color='DimGrey'>one of the CH domains of alpha-actinin 3</font> ([[1wku]]) is performed, a good overall overlap is observed, as represented by the RMSD of 1.19 Å for 103 equivalent C<sup>α</sup> positions, despite low sequence homology (≤26% identity).<ref>PMID: 18940607</ref> Again the best overlap is seen for the core helices. This suggests that the structural framework of CH domain and its core in particular are quite robust under evolution.
+[[Image:Consurf_key_small.gif|right|200px]]The scene on the left shows the structure of the <scene name='Alpha-parvin/Parvin/9'>C-terminal CH domain of alpha-parvin</scene> at around 1.05 Å ([[2vzc]]). When a sequence alignment of alpha-parvin with all its sequence homologues is performed and the protein is coloured according to <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin/3'>the degree of sequence conservation</scene>, one can see that the highest degree of conservation is exhibited by the residues located in <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin/5'>the core helices</scene>, while the residues in linker helices and loops are less conserved. When the <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin_overlap/1'>structural superposition</scene> of the <font color='brown'>C-terminal CH domain of alpha-parvin</font> and <font color='DimGrey'>one of the CH domains of alpha-actinin 3</font> ([[1wku]]) is performed, a good overall overlap is observed, as represented by the RMSD of 1.19 Å for 103 equivalent C<sup>α</sup> positions, despite low sequence homology (≤26% identity).<ref>PMID: 18940607</ref> Again the best overlap is seen for the core helices. This suggests that the structural framework of CH domain and its core in particular are quite robust under evolution.
-The most diverged fragments in the C-terminal CH domain of alpha-parvin correspond to 1) an <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin_overlap/3'>additional helix</scene> (so called N-terminal linker helix; it is labelled αN in the picture above on the right) located at the N-terminal end of the domain and not observed in any other CH domain and 2) a <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin_overlap/5'>long loop</scene> between two helices (which are labelled αC and αE in the picture above on the right). One could ask whether the N-terminal linker helix is an integral part of the C-terminal CH domain or just a part of a linker region between the two CH domains. The fact that it interacts strongly with the core helices by means of both electrostatic (<scene name='Alpha-parvin/Parvin_overlap/1'>residues D248, D251 and D255 with K355 and R359</scene>) and hydrophobic (<scene name='Alpha-parvin/Parvin_overlap/4'>residues F250, L253 and F254 with L354, K355, L358, R359, K260 and L261</scene>) interactions suggests that it is indeed integral to the domain. The long loop mentioned above contains a <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin_overlap/6'>3-amino acid insertion</scene> (313-315) relative to other known CH domains and differs in conformation between different structures of alpha-parvin, suggesting it is relatively flexible.<ref>PMID: 18940607</ref> Interestingly, these two regions, the N-terminal linker helix and the long loop, are involved in binding of alpha-parvin to its binding partners, paxillin and ILK respectively.
+The most diverged fragments in the C-terminal CH domain of alpha-parvin correspond to 1) an <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin_overlap/3'>additional helix</scene> (so called N-terminal linker helix; it is labelled αN or helix N) located at the N-terminal end of the domain and not observed in any other CH domain and 2) a <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin_overlap/5'>long loop</scene> between two helices (αC and αE). One could ask whether the N-terminal linker helix is an integral part of the C-terminal CH domain or just a part of a linker region between the two CH domains. The fact that it interacts strongly with the core helices by means of both electrostatic (<scene name='Alpha-parvin/Parvin_overlap/1'>residues D248, D251 and D255 with K355 and R359</scene>) and hydrophobic (<scene name='Alpha-parvin/Parvin_overlap/4'>residues F250, L253 and F254 with L354, K355, L358, R359, K260 and L261</scene>) interactions suggests that it is indeed integral to the domain. The long loop mentioned above contains a <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_Parvin//Parvin_overlap/6'>3-amino acid insertion</scene> (313-315) relative to other known CH domains and differs in conformation between different structures of alpha-parvin, suggesting it is relatively flexible.<ref>PMID: 18940607</ref> Interestingly, these two regions, the N-terminal linker helix and the long loop, are involved in binding of alpha-parvin to its binding partners, paxillin and ILK respectively.
 <Structure load='Complex_parvin.pdb' size='340' scene='Alpha-parvin/Parvin/2' frame='true' align='right' caption='The alignment of three C-terminal CH domains of alpha-parvin bound to different paxillin LD motifs ([[2vzd]], [[2vzg]], [[2vzi]])'/>