View source for 7mzt


==Borrelia burgdorferi BBK32-C in complex with an autolytic fragment of human C1r at 4.1A==
<StructureSection load='7mzt' size='340' side='right'caption='[[7mzt]], [[Resolution|resolution]] 4.07&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7mzt]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Borreliella_burgdorferi_B31 Borreliella burgdorferi B31] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MZT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MZT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.07&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7mzt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mzt OCA], [https://pdbe.org/7mzt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mzt RCSB], [https://www.ebi.ac.uk/pdbsum/7mzt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mzt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C1R_HUMAN C1R_HUMAN] C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Complement evasion is a hallmark of extracellular microbial pathogens such as Borrelia burgdorferi, the causative agent of Lyme disease. Lyme disease spirochetes express nearly a dozen outer surface lipoproteins that bind complement components and interfere with their native activities. Among these, BBK32 is unique in its selective inhibition of the classical pathway. BBK32 blocks activation of this pathway by selectively binding and inhibiting the C1r serine protease of the first component of complement, C1. To understand the structural basis for BBK32-mediated C1r inhibition, we performed crystallography and size-exclusion chromatography-coupled small angle X-ray scattering experiments, which revealed a molecular model of BBK32-C in complex with activated human C1r. Structure-guided site-directed mutagenesis was combined with surface plasmon resonance binding experiments and assays of complement function to validate the predicted molecular interface. Analysis of the structures shows that BBK32 inhibits activated forms of C1r by occluding substrate interaction subsites (i.e., S1 and S1') and reveals a surprising role for C1r B loop-interacting residues for full inhibitory activity of BBK32. The studies reported in this article provide for the first time (to our knowledge) a structural basis for classical pathway-specific inhibition by a human pathogen.

A Structural Basis for Inhibition of the Complement Initiator Protease C1r by Lyme Disease Spirochetes.,Garrigues RJ, Powell-Pierce AD, Hammel M, Skare JT, Garcia BL J Immunol. 2021 Dec 1;207(11):2856-2867. doi: 10.4049/jimmunol.2100815. Epub 2021 , Nov 10. PMID:34759015<ref>PMID:34759015</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7mzt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Borreliella burgdorferi B31]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Garcia BL]]