Journal:Acta Cryst D:S2059798324007733
From Proteopedia
(Difference between revisions)
| (51 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | <StructureSection load='' size='450' side='right' scene='10/1055499/ | + | <StructureSection load='' size='450' side='right' scene='10/1055499/8vo1_nowat_pdb/3' caption='3D structure pf pathogenesis-related family 10, specifically PR10-10-Cys155Ser (PDB-ID [[8vo1]]).'> |
===Structural analysis of a ligand-triggered intermolecular disulfide switch in a major latex protein from opium poppy=== | ===Structural analysis of a ligand-triggered intermolecular disulfide switch in a major latex protein from opium poppy=== | ||
<big>Samuel C. Carr, Peter J. Facchini, Kenneth K.S. Ng</big><ref>PMID:39207895</ref> | <big>Samuel C. Carr, Peter J. Facchini, Kenneth K.S. Ng</big><ref>PMID:39207895</ref> | ||
<hr/> | <hr/> | ||
<b>Molecular Tour</b><br> | <b>Molecular Tour</b><br> | ||
| - | Pathogenesis related 10 proteins have | + | Pathogenesis related 10 proteins have been shown to bind the alkaloids of opium poppy and are suspected to be involved in their storage in the latex of specialized cells called ‘laticifers’. PR10-10 is a highly abundant protein in the latex of opium poppy and is known to bind alkaloids such as papaverine. The crystal structure of PR10-10 reveals how the binding of papaverine to the central hydrophobic cavity of the protein leads to large conformational changes in the structure of PR10-10. Binding of papaverine leads to the ordering of the cap-loop which sequesters the bound alkaloid. Ordering of the cap-loop changes the shape and size of the central cavity though the partial unwinding of an alpha-helix and ordering of a beta-strand. Beta-strand ordering leads to the burying of a cysteine sidechain which otherwise forms an intermolecular disulfide bond with other PR10-10 proteins. The structure of three cysteine to serine mutants of PR10-10 further demonstrate the importance of the intermolecular disulfide bond. When the disulfide bond forming cysteines 59 and 155 in PR10-10 are mutated to serine, thus unable to form disulfide bonds, the cap-loop of PR10-10 remains ordered, and the central cavity always occupied by a ligand. This demonstrates how the presence of the alkaloid changes not only the local structure of PR10-10 but also its ability to interact more widely with nearby proteins. The formation of intermolecular disulfide bonds in PR10-10 is predicted to be coupled to the large-scale organization of PR10 proteins and subsequent storage of high concentrations of alkaloids within protein aggregates in the latex of opium poppy. |
| + | <br> | ||
| + | The novel crystal structures of the <scene name='10/1055499/8vo1_nowat_pdb/2'>Cys59Ser</scene> and <scene name='10/1055499/8vo2_nowat_pdb/3'>Cys155Ser</scene> mutants are remakably similar to the <scene name='10/1055499/8vo3_nowat_pdb/2'>BIA bounf WT</scene> structure. This cam be seem om the <scene name='10/1055499/Superposition/2'>superposition</scene> of the three structures and in an <scene name='10/1055499/Animation/7'>animation</scene> <jmol><jmolButton> | ||
| + | <script>animation off</script> | ||
| + | <text>animation off</text> | ||
| + | </jmolButton> | ||
| + | </jmol>. This helps to further define the role of the disulfide bond in stabilizing a ligand-free apo conformation that is disfavoured in both mutants. | ||
<br> | <br> | ||
| - | The novel crystal structures of the Cys59Ser and Cys155Ser mutants help to further define the role of the disulfide bond in stabilizing a ligand-free apo conformation that is disfavoured in both mutants. In fact the <scene name='10/1055499/8ov1_8ov2_8vo3/4'>two mutated structures are remarkably similar to the BIA bound WT structure</scene>. | ||
| - | |||
| - | <jmol> | ||
| - | |||
| - | <jmolButton> | ||
| - | <script> | ||
| - | if (sf!='8c4ab271d907ea46ee5b7043bfa8c37d') { | ||
| - | load /*file*/"/cgi-bin/getfrozenstructure?8c4ab271d907ea46ee5b7043bfa8c37d"; | ||
| - | sf = '8c4ab271d907ea46ee5b7043bfa8c37d'; delete water; | ||
| - | script /wiki/extensions/Proteopedia/spt/initialview03.spt; color structure; spin off; | ||
| - | } | ||
| - | model 1; | ||
| - | script "/cgi-bin/pprcpt?The structure of mutant C155S [[8vo1]] is strikingly similar to the WT apo_PR10-10 bound with papaverine [[8vo3]]."; | ||
| - | </script> | ||
| - | <text>mutant C155S</text> | ||
| - | </jmolButton> | ||
| - | |||
| - | <jmolButton> | ||
| - | <script> | ||
| - | if (sf!='8c4ab271d907ea46ee5b7043bfa8c37d') { | ||
| - | load /*file*/"/cgi-bin/getfrozenstructure?8c4ab271d907ea46ee5b7043bfa8c37d"; | ||
| - | sf = '8c4ab271d907ea46ee5b7043bfa8c37d'; delete water; | ||
| - | script /wiki/extensions/Proteopedia/spt/initialview03.spt; color structure; spin off; | ||
| - | } | ||
| - | model 2; | ||
| - | script "/cgi-bin/pprcpt?The structure of mutant C59S [[8vo2]] is strikingly similar to the WT apo_PR10-10 bound with papaverine [[8vo3]]."; | ||
| - | </script> | ||
| - | <text>mutant C59S</text> | ||
| - | </jmolButton> | ||
| - | |||
| - | <jmolButton> | ||
| - | <script> | ||
| - | if (sf!='8c4ab271d907ea46ee5b7043bfa8c37d') { | ||
| - | load /*file*/"/cgi-bin/getfrozenstructure?8c4ab271d907ea46ee5b7043bfa8c37d"; | ||
| - | sf = '8c4ab271d907ea46ee5b7043bfa8c37d'; delete water; | ||
| - | script /wiki/extensions/Proteopedia/spt/initialview03.spt; color structure; spin off; | ||
| - | } | ||
| - | model 3; | ||
| - | script "/cgi-bin/pprcpt?The structure of the WT apo_PR10-10 bound with papaverine [[8vo3]]."; | ||
| - | </script> | ||
| - | <text>WT bound with papaverine</text> | ||
| - | </jmolButton> | ||
| - | |||
| - | <jmolButton> | ||
| - | <script> | ||
| - | if (sf!='8c4ab271d907ea46ee5b7043bfa8c37d') { | ||
| - | load /*file*/"/cgi-bin/getfrozenstructure?8c4ab271d907ea46ee5b7043bfa8c37d"; | ||
| - | sf = '8c4ab271d907ea46ee5b7043bfa8c37d'; delete water; | ||
| - | script /wiki/extensions/Proteopedia/spt/initialview03.spt; color structure; spin off; | ||
| - | } | ||
| - | model 0; | ||
| - | script "/cgi-bin/pprcpt?The structure of the WT apo_PR10-10 bound with papaverine [[8vo3]]."; | ||
| - | </script> | ||
| - | <text>Three structures superimposed</text> | ||
| - | </jmolButton> | ||
| - | |||
| - | </jmol> | ||
| - | |||
| - | |||
<b>References</b><br> | <b>References</b><br> | ||
<references/> | <references/> | ||
</StructureSection> | </StructureSection> | ||
__NOEDITSECTION__ | __NOEDITSECTION__ | ||
Current revision
| |||||||||||
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.
