Journal:Acta Cryst D:S2059798322011639
From Proteopedia
(Difference between revisions)
| Line 8: | Line 8: | ||
Recent reports from the Markley Lab (Cai, 2018) confirmed that Fe(II) is delivered by frataxin to the scaffold in the presence of ferredoxin; ferredoxin within the pathway provides reducing equivalents for cluster assembly. Previous reports (Kondapalli, 2008; Koebke, 2019) confirmed the binding affinities of Fe(II) to frataxin orthologs of yeast (''Saccharomyces cerevisiae'') and flies (''Drosophila melanogaster''). In Drosophila frataxin (Dfh), which has shown increased stability relative to its orthologs, iron binds within the micromolar affinity range. Other frataxin orthologs also bind in this range and these affinities are within the range of available Fe(II) in the mitochondria. This suggests that Dfh is loaded with Fe(II) while in the cellular mitochondrial matrix. Based on the iron binding capability of Dfh with respect to Fe-S cluster assembly and its increased stability, this report characterizes the crystal and solution state structures of Dfh and highlights likely Fe-binding residues. | Recent reports from the Markley Lab (Cai, 2018) confirmed that Fe(II) is delivered by frataxin to the scaffold in the presence of ferredoxin; ferredoxin within the pathway provides reducing equivalents for cluster assembly. Previous reports (Kondapalli, 2008; Koebke, 2019) confirmed the binding affinities of Fe(II) to frataxin orthologs of yeast (''Saccharomyces cerevisiae'') and flies (''Drosophila melanogaster''). In Drosophila frataxin (Dfh), which has shown increased stability relative to its orthologs, iron binds within the micromolar affinity range. Other frataxin orthologs also bind in this range and these affinities are within the range of available Fe(II) in the mitochondria. This suggests that Dfh is loaded with Fe(II) while in the cellular mitochondrial matrix. Based on the iron binding capability of Dfh with respect to Fe-S cluster assembly and its increased stability, this report characterizes the crystal and solution state structures of Dfh and highlights likely Fe-binding residues. | ||
| - | In this study, we found that all frataxin orthologs are very similar in structure as expected from their comparative amino acid sequence alignment. However, this structural similarity does not translate to protein stability. <scene name='94/942632/Cv/2'>The X-ray crystal structure of Dfh</scene>, at a resolution of 1.4 Å, is a well-folded protein with a conserved αβ-sandwich motif with two α-helices, six β-sheets, and a 3<sub>10</sub>-helix on the C-terminal tail. Labels for the different secondary structural elements are marked on the corresponding helix or strand (PDB ID: [[7n9i]]). <scene name='94/942632/Cv/3'>Protein charge</scene>. <span class="bg-yellow"><span class="far fa-hand-point-right"></span> Remember to drag the structures with the mouse to rotate them.</span>. The solution structure, which is highly similar, has minor differences in the length of the N-terminal tail and β-sheets, and the helix of the C-terminal tail is absent; differences likely due to crystal packing. Potential Fe-binding residues on Dfh were identified by nuclear magnetic resonance in the presence of Fe(II). Of the 133 residues in Dfh, 8 were perturbed, beyond the threshold, in the presence of iron. The residues are predominantly acidic and in the same region as seen in frataxin orthologs. | + | In this study, we found that all frataxin orthologs are very similar in structure as expected from their comparative amino acid sequence alignment. However, this structural similarity does not translate to protein stability. <scene name='94/942632/Cv/2'>The X-ray crystal structure of Dfh</scene>, at a resolution of 1.4 Å, is a well-folded protein with a conserved αβ-sandwich motif with two α-helices, six β-sheets, and a 3<sub>10</sub>-helix on the C-terminal tail. Labels for the different secondary structural elements are marked on the corresponding helix or strand (PDB ID: [[7n9i]]). <scene name='94/942632/Cv/3'>Protein charge is shown</scene>. <span class="bg-yellow"><span class="far fa-hand-point-right"></span> Remember to drag the structures with the mouse to rotate them.</span>. The solution structure, which is highly similar, has minor differences in the length of the N-terminal tail and β-sheets, and the helix of the C-terminal tail is absent; differences likely due to crystal packing. Potential Fe-binding residues on Dfh were identified by nuclear magnetic resonance in the presence of Fe(II). Of the 133 residues in Dfh, 8 were perturbed, beyond the threshold, in the presence of iron. The residues are predominantly acidic and in the same region as seen in frataxin orthologs. |
<b>References</b><br> | <b>References</b><br> | ||
Revision as of 11:42, 21 December 2022
| |||||||||||
This page complements a publication in scientific journals and is one of the Proteopedia's Interactive 3D Complement pages. For aditional details please see I3DC.
