Recoverin, a calcium-activated myristoyl switch: Difference between revisions
Michal Harel (talk | contribs) No edit summary |
No edit summary |
||
| (12 intermediate revisions by 4 users not shown) | |||
| Line 1: | Line 1: | ||
<StructureSection load=' | <StructureSection load='' size='350' side='right' scene='Recoverin,_a_calcium-activated_myristoyl_switch/Recoverin_morph/2' caption='Recoverin: [[1iku]] model 7 (calcium-free) morphed to [[1jsa]] model 9 (calcium-bound) complex with myristic acid.' > | ||
==Function== | ==Function== | ||
| Line 7: | Line 7: | ||
==Myristoyl Switch and Calcium== | ==Myristoyl Switch and Calcium== | ||
<scene name='Recoverin,_a_calcium-activated_myristoyl_switch/Recoverin_no_calcium/2'>Recoverin</scene> (Initial colors: '''<font color="#808080">Hydrophobic</font>, <font color="#e000e0">Polar</font>''') has a <scene name='Recoverin,_a_calcium-activated_myristoyl_switch/Recoverin_morph/5'>myristic acid</scene> (14-carbon saturated fatty acid, or a similar acyl moiety) covalently linked via an amide bond to its N-terminal glycine. In the absence of calcium, the <scene name='Recoverin,_a_calcium-activated_myristoyl_switch/Recoverin_no_calcium/1'>myristoyl group is buried</scene> in the N-terminal protein domain, surrounded on all sides by alpha helices that form a hydrophobic pocket. The binding of <scene name='Recoverin,_a_calcium-activated_myristoyl_switch/Recoverin_morph/6'>two calcium ions</scene> to each recoverin molecule induces a <scene name='Recoverin,_a_calcium-activated_myristoyl_switch/Recoverin_morph/1'>conformational change </scene> that extrudes the myristoyl and exposes some hydrophobic amino acids on the surface. This enables the molecule to bind to the lipid bilayers of the disc membranes. | <scene name='Recoverin,_a_calcium-activated_myristoyl_switch/Recoverin_no_calcium/2'>Recoverin</scene> (Initial colors: '''<font color="#808080">Hydrophobic</font>, <font color="#e000e0">Polar</font>''') has a <scene name='Recoverin,_a_calcium-activated_myristoyl_switch/Recoverin_morph/5'>myristic acid</scene> (14-carbon saturated fatty acid, or a similar acyl moiety) covalently linked via an amide bond to its N-terminal glycine. In the absence of calcium, the <scene name='Recoverin,_a_calcium-activated_myristoyl_switch/Recoverin_no_calcium/1'>myristoyl group is buried</scene> in the N-terminal protein domain, surrounded on all sides by alpha helices that form a hydrophobic pocket. The binding of <scene name='Recoverin,_a_calcium-activated_myristoyl_switch/Recoverin_morph/6'>two calcium ions</scene> to each recoverin molecule induces a <scene name='Recoverin,_a_calcium-activated_myristoyl_switch/Recoverin_morph/1'>conformational change </scene> that extrudes the myristoyl and exposes some hydrophobic amino acids on the surface. This enables the molecule to bind to the lipid bilayers of the disc membranes. <scene name='24/241531/Recoverin_storymorph/1'>An alternate morph</scene> <ref>The [[Jmol/Storymorph|Storymorph Jmol scripts]] were used to create the interpolation shown in the morph. [https://proteopedia.org/wiki/index.php/Image:Morph_recoverin.pdb Coordinates] available on Proteopedia</ref> emphasizes that two parts of the molecule rotate relative to each other while retaining their local fold. | ||
{{Template:Button Toggle Animation2}} | |||
The two calcium ions each bind to an EF hand motif, one in the C-terminal domain, and one in the N-terminal domain. Recoverin actually contains four EF hand motifs, but two of them are unable to bind calcium due to variations in sequence. | The two calcium ions each bind to an EF hand motif, one in the C-terminal domain, and one in the N-terminal domain. Recoverin actually contains four EF hand motifs, but two of them are unable to bind calcium due to variations in sequence. | ||
| Line 17: | Line 19: | ||
Recoverin was the first member of the calcium-myristoyl switch family family whose 3D structure was determined. The structure of the calcium-free form was determined by solution NMR in 1995<ref name="tanaka1995"/>. Determination of the calcium-bound, hydrophobic form by solution NMR required modification of the myristoyl: carbon in the 13th position was replaced with oxygen (Ames et al., 1997<ref>Ames JB, Ishima R, Tanaka T, Gordon JI, Stryer L, Ikura M, Nature 389(6647):198-202, 1997. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9296500 9296500]</ref>). The 13-oxa myristoyl analog recoverin retains a functional calcium-myristoyl switch, and the calcium-bound conformation is very similar to the natural form (by heteronuclear single quantum coherence spectra). | Recoverin was the first member of the calcium-myristoyl switch family family whose 3D structure was determined. The structure of the calcium-free form was determined by solution NMR in 1995<ref name="tanaka1995"/>. Determination of the calcium-bound, hydrophobic form by solution NMR required modification of the myristoyl: carbon in the 13th position was replaced with oxygen (Ames et al., 1997<ref>Ames JB, Ishima R, Tanaka T, Gordon JI, Stryer L, Ikura M, Nature 389(6647):198-202, 1997. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9296500 9296500]</ref>). The 13-oxa myristoyl analog recoverin retains a functional calcium-myristoyl switch, and the calcium-bound conformation is very similar to the natural form (by heteronuclear single quantum coherence spectra). | ||
The Morphs provided here illustrate the structural relationships between the calcium-free, water-soluble conformation, and the calcium-bound, hydrophobic conformation. | The [[Morphs]] provided here illustrate the structural relationships between the calcium-free, water-soluble conformation, and the calcium-bound, hydrophobic conformation. | ||
==Technical Notes== | ==Technical Notes== | ||
Both 1iku and 1jsa are ensembles of NMR models. The morph is a [[Morphs |linear interpolation morph]] between model 7 and model 9, respectively. Only the alpha carbon atoms of the protein are present in the morph PDB file. For the space-filled model 7 of 1iku, hydrogen atoms were deleted except for those in the myristoyl adduct. | Both 1iku and 1jsa are ensembles of NMR models. The morph is a [[Morphs |linear interpolation morph]] between model 7 and model 9, respectively. Only the alpha carbon atoms of the protein are present in the morph PDB file. For the space-filled model 7 of 1iku, hydrogen atoms were deleted except for those in the myristoyl adduct. The alternate morph preserving rigid domains was created using the [[Jmol/Storymorph|Storymorph Jmol scripts]]. | ||
</StructureSection> | </StructureSection> | ||
__NOTOC__ | __NOTOC__ | ||
| Line 30: | Line 32: | ||
[[2het]], [[1omr]], [[1rec]], [[4m2q]], [[4mlw]] – bRCV – bovine<br /> | [[2het]], [[1omr]], [[1rec]], [[4m2q]], [[4mlw]] – bRCV – bovine<br /> | ||
[[1jsa]], [[1iku]] - bRCV - NMR<br /> | [[1jsa]], [[1iku]] - bRCV - NMR<br /> | ||
[[1omv]], [[4m2o]], [[4m2p]] – bRCV (mutant)<br /> | [[1omv]], [[4m2o]], [[4m2p]], [[4yi8]], [[4yi9]] – bRCV (mutant)<br /> | ||
[[1la3]] - bRCV (mutant) - NMR<br /> | [[1la3]] - bRCV (mutant) - NMR<br /> | ||
[[2i94]] – bRCV + rhodopsin kinase | [[2i94]] – bRCV + rhodopsin kinase | ||