7s0r: Difference between revisions
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==Crystal Structure of a Complement Factor H-binding Fragment within the B75KN Region of the Group B Streptococcus Beta Antigen C Protein== | |||
<StructureSection load='7s0r' size='340' side='right'caption='[[7s0r]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7s0r]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7S0R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S0R FirstGlance]. <br> | |||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=7s0r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s0r OCA], [https://pdbe.org/7s0r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s0r RCSB], [https://www.ebi.ac.uk/pdbsum/7s0r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s0r ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The beta protein from group B Streptococcus (GBS) is a approximately 132-kDa, cell-surface exposed molecule that binds to multiple host-derived ligands, including complement factor H (FH). Many details regarding this interaction and its significance to immune evasion by GBS remain unclear. In this study, we identified a three-helix bundle domain within the C-terminal half of the B75KN region of beta as the major FH-binding determinant and determined its crystal structure at 2.5 A resolution. Analysis of this structure suggested a role in FH binding for a loop region connecting helices alpha1 and alpha2, which we confirmed by mutagenesis and direct binding studies. Using a combination of protein cross-linking and mass spectrometry, we observed that B75KN bound to complement control protein (CCP)3 and CCP4 domains of FH. Although this binding site lies within a complement regulatory region of FH, we determined that FH bound by beta retained its decay acceleration and cofactor activities. Heterologous expression of beta by Lactococcus lactis resulted in recruitment of FH to the bacterial surface and a significant reduction of C3b deposition following exposure to human serum. Surprisingly, we found that FH binding by beta was not required for bacterial resistance to phagocytosis by neutrophils or killing of bacteria by whole human blood. However, loss of the B75KN region significantly diminished bacterial survival in both assays. Although our results show that FH recruited to the bacterial surface through a high-affinity interaction maintains key complement-regulatory functions, they raise questions about the importance of FH binding to immune evasion by GBS as a whole. | |||
Group B Streptococcus Surface Protein beta: Structural Characterization of a Complement Factor H-Binding Motif and Its Contribution to Immune Evasion.,Xu X, Lewis Marffy AL, Keightley A, McCarthy AJ, Geisbrecht BV J Immunol. 2022 Mar 1;208(5):1232-1247. doi: 10.4049/jimmunol.2101078. Epub 2022 , Feb 2. PMID:35110419<ref>PMID:35110419</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7s0r" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Geisbrecht, B V]] | |||
[[Category: Xu, X]] | |||
[[Category: Cell-surface protein]] | |||
[[Category: Complement]] | |||
[[Category: Factor h]] | |||
[[Category: Immune evasion]] | |||
[[Category: Protein binding]] | |||
Latest revision as of 10:33, 29 June 2022
Crystal Structure of a Complement Factor H-binding Fragment within the B75KN Region of the Group B Streptococcus Beta Antigen C ProteinCrystal Structure of a Complement Factor H-binding Fragment within the B75KN Region of the Group B Streptococcus Beta Antigen C Protein
Structural highlights
Publication Abstract from PubMedThe beta protein from group B Streptococcus (GBS) is a approximately 132-kDa, cell-surface exposed molecule that binds to multiple host-derived ligands, including complement factor H (FH). Many details regarding this interaction and its significance to immune evasion by GBS remain unclear. In this study, we identified a three-helix bundle domain within the C-terminal half of the B75KN region of beta as the major FH-binding determinant and determined its crystal structure at 2.5 A resolution. Analysis of this structure suggested a role in FH binding for a loop region connecting helices alpha1 and alpha2, which we confirmed by mutagenesis and direct binding studies. Using a combination of protein cross-linking and mass spectrometry, we observed that B75KN bound to complement control protein (CCP)3 and CCP4 domains of FH. Although this binding site lies within a complement regulatory region of FH, we determined that FH bound by beta retained its decay acceleration and cofactor activities. Heterologous expression of beta by Lactococcus lactis resulted in recruitment of FH to the bacterial surface and a significant reduction of C3b deposition following exposure to human serum. Surprisingly, we found that FH binding by beta was not required for bacterial resistance to phagocytosis by neutrophils or killing of bacteria by whole human blood. However, loss of the B75KN region significantly diminished bacterial survival in both assays. Although our results show that FH recruited to the bacterial surface through a high-affinity interaction maintains key complement-regulatory functions, they raise questions about the importance of FH binding to immune evasion by GBS as a whole. Group B Streptococcus Surface Protein beta: Structural Characterization of a Complement Factor H-Binding Motif and Its Contribution to Immune Evasion.,Xu X, Lewis Marffy AL, Keightley A, McCarthy AJ, Geisbrecht BV J Immunol. 2022 Mar 1;208(5):1232-1247. doi: 10.4049/jimmunol.2101078. Epub 2022 , Feb 2. PMID:35110419[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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