Parvin: Difference between revisions
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===ILK binding=== | ===ILK binding=== | ||
The <scene name='Alpha-parvin/Ilk_parvin/1'>scene on the left</scene> shows the complex ([[3kmw]]) of the kinase domain of integrin-linked kinase (ILK, red) bound to the C-terminal CH domain of alpha-parvin (blue). One can also see the molecule of ATP (green) and the space-fill representation of the magnesium atom (white). When we <scene name='Alpha-parvin/Ilk_parvin/2'>turn the structure</scene> so that the N-terminal helix (now orange) of the CH domain of alpha-parvin is pointing up, we can see that unlike paxillin LD motifs, ILK kinase domain does not bind to the N-terminal region of the CH domain, but rather near the <scene name='Alpha-parvin/Ilk_parvin/3'>long loop</scene> between helices αC and αE. Other parts of the CH domain are also involved in binding, leading to a high interface area (around 1900 Å<sup>2</sup>) characteristic of high-affinity complexes.<ref>PMID:20005845</ref> Interestingly, ILK, which was recently proved to lack kinase activity<ref>PMID:20005845</ref><ref>PMID: 20033063</ref>, binds alpha-parvin analogously to the way in which kinases bind their substrates, i.e. with its pseudoactive site. The binding is not dependent on the presence of ATP. On the ILK's side the binding is mediated primarily by <scene name='Alpha-parvin/Ilk_parvin/6'>one of the helices</scene> (αG) and a <scene name='Alpha-parvin/Ilk_parvin/5'>part of the activation loop</scene>. The complex formation is particularly dependent on <scene name='Alpha-parvin/Ilk_parvin/7'>methionine 402 and lysine 403</scene> in αG of ILK - if these two residues are mutated to alanines, the complex formation is completely abolished. These residues are involved in many interactions with alpha-parvin (one of them, a hydrogen bond to asparagine 280, is shown) or water molecules (one of them shown as a pink dot). | The <scene name='Alpha-parvin/Ilk_parvin/1'>scene on the left</scene> shows the complex ([[3kmw]]) of the kinase domain of integrin-linked kinase (ILK, red) bound to the C-terminal CH domain of alpha-parvin (blue). One can also see the molecule of ATP (green) and the space-fill representation of the magnesium atom (white). When we <scene name='Alpha-parvin/Ilk_parvin/2'>turn the structure</scene> so that the N-terminal helix (now orange) of the CH domain of alpha-parvin is pointing up, we can see that unlike paxillin LD motifs, ILK kinase domain does not bind to the N-terminal region of the CH domain, but rather near the <scene name='Alpha-parvin/Ilk_parvin/3'>long loop</scene> between helices αC and αE. Other parts of the CH domain are also involved in binding, leading to a high interface area (around 1900 Å<sup>2</sup>) characteristic of high-affinity complexes.<ref>PMID:20005845</ref> Interestingly, ILK, which was recently proved to lack kinase activity<ref>PMID:20005845</ref><ref>PMID: 20033063</ref>, binds alpha-parvin analogously to the way in which kinases bind their substrates, i.e. with its pseudoactive site. The binding is not dependent on the presence of ATP. On the ILK's side the binding is mediated primarily by <scene name='Alpha-parvin/Ilk_parvin/6'>one of the helices</scene> (αG) and a <scene name='Alpha-parvin/Ilk_parvin/5'>part of the activation loop</scene>. The complex formation is particularly dependent on <scene name='Alpha-parvin/Ilk_parvin/7'>methionine 402 and lysine 403</scene> in αG of ILK - if these two residues are mutated to alanines, the complex formation is completely abolished. These residues are involved in many interactions with alpha-parvin (one of them, a hydrogen bond to asparagine 280, is shown) or water molecules (one of them shown as a pink dot). | ||
==3D structures of Alpha-parvin== | ==3D structures of Alpha-parvin== | ||