|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Solution structure of VKK38 bound to plasminogen kringle 2== | | ==Solution structure of VKK38 bound to plasminogen kringle 2== |
| - | <StructureSection load='5v4u' size='340' side='right' caption='[[5v4u]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='5v4u' size='340' side='right'caption='[[5v4u]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5v4u]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V4U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V4U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5v4u]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pyogenes Streptococcus pyogenes]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V4U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V4U FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2kj4|2kj4]], [[5v4z|5v4z]]</td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5v4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v4u OCA], [https://pdbe.org/5v4u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v4u RCSB], [https://www.ebi.ac.uk/pdbsum/5v4u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v4u ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5v4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v4u OCA], [http://pdbe.org/5v4u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v4u RCSB], [http://www.ebi.ac.uk/pdbsum/5v4u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v4u ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q54839_STRPY Q54839_STRPY] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 20: |
Line 21: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Castellino, F]] | + | [[Category: Large Structures]] |
| - | [[Category: Yuan, Y]] | + | [[Category: Streptococcus pyogenes]] |
| - | [[Category: Blood clotting]] | + | [[Category: Castellino F]] |
| - | [[Category: Protein/peptide]] | + | [[Category: Yuan Y]] |
| Structural highlights
Function
Q54839_STRPY
Publication Abstract from PubMed
The binding of human plasminogen (hPg) to the surface of the human pathogen Streptococcus pyogenes (GAS) and subsequent hPg activation to the protease plasmin generate a proteolytic surface that GAS employs to circumvent host innate immunity. Direct high-affinity binding of hPg/plasmin to pattern D GAS is fully recapitulated by the hPg kringle 2 domain (K2hPg) and a short internal peptide region (a1a2) of a specific subtype of bacterial surface M protein, present in all GAS pattern D strains. To better understand the nature of this binding, critical to the virulence of many GAS skin-tropic strains, we used high-resolution NMR to define the interaction of recombinant K2hPg with recombinant a1a2 (VKK38) of the M protein from GAS isolate NS455. We found a 2:1 (m:m) binding stoichiometry of K2hPg:VKK38, with the lysine-binding sites of two K2hPg domains anchored to two regions of monomeric VKK38. The K2hPg/VKK38 binding altered the VKK38 secondary structure from a helical apo-peptide with a flexible center to an end-to-end K2hPg-bound alpha-helix. The K2hPg residues occupied opposite faces of this helix, an arrangement that minimized steric clashing of K2hPg. We conclude that VKK38 provides two conformational lysine isosteres that each interact with the lysine binding sites in K2hPg. Further, the adoption of an alpha-helix by VKK38 upon binding to K2hPg sterically optimizes the side chains of VKK38 for maximal binding to K2hPg and minimizes steric overlap between the K2hPg domains. The mechanism for hPg/M protein binding uncovered here may facilitate targeting of GAS virulence factors for disease management.
Conformationally Organized Lysine Isosteres in Streptococcus Pyogenes M Protein Mediate Direct High-Affinity Binding to Human Plasminogen.,Yuan Y, Zajicek J, Qiu C, Chandrahas V, Lee SW, Ploplis VA, Castellino FJ J Biol Chem. 2017 Jul 19. pii: jbc.M117.794198. doi: 10.1074/jbc.M117.794198. PMID:28724633[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yuan Y, Zajicek J, Qiu C, Chandrahas V, Lee SW, Ploplis VA, Castellino FJ. Conformationally Organized Lysine Isosteres in Streptococcus Pyogenes M Protein Mediate Direct High-Affinity Binding to Human Plasminogen. J Biol Chem. 2017 Jul 19. pii: jbc.M117.794198. doi: 10.1074/jbc.M117.794198. PMID:28724633 doi:http://dx.doi.org/10.1074/jbc.M117.794198
|
