View source for 2yby


==Structure of domains 6 and 7 of the mouse complement regulator Factor H==
<StructureSection load='2yby' size='340' side='right'caption='[[2yby]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2yby]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YBY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YBY 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]] 1.58&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=2yby FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yby OCA], [https://pdbe.org/2yby PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yby RCSB], [https://www.ebi.ac.uk/pdbsum/2yby PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yby ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CFAH_MOUSE CFAH_MOUSE] Factor H functions as a cofactor in the inactivation of C3b by factor I and also increases the rate of dissociation of the C3bBb complex (C3 convertase) and the (C3b)NBB complex (C5 convertase) in the alternative complement pathway.
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== Publication Abstract from PubMed ==
Neisseria meningitis remains a leading cause of sepsis and meningitis, and vaccines are required to prevent infections by this important human pathogen. Factor H binding protein (fHbp) is a key antigen that elicits protective immunity against the meningococcus and recruits the host complement regulator, fH. As the high affinity interaction between fHbp and fH could impair immune responses, we sought to identify non-functional fHbps that could act as effective immunogens. This was achieved by alanine substitution of fHbps from all three variant groups (V1, V2 and V3 fHbp) of the protein; while some residues affected fH binding in each variant group, the distribution of key amino underlying the interaction with fH differed between the V1, V2 and V3 proteins. The atomic structure of V3 fHbp in complex with fH and of the C-terminal barrel of V2 fHbp provide explanations to the differences in the precise nature of their interactions with fH, and the instability of the V2 protein. To develop transgenic models to assess the efficacy of non-functional fHbps, we determined the structural basis of the low level of interaction between fHbp and murine fH; in addition to changes in amino acids in the fHbp binding site, murine fH has a distinct conformation compared with the human protein that would sterically inhibit binding to fHbp. Non-functional V1 fHbps were further characterised by binding and structural studies, and shown in non-transgenic and transgenic mice (expressing chimeric fH that binds fHbp and precisely regulates complement system) to retain their immunogenicity. Our findings provide a catalogue of non-functional fHbps from all variant groups that can be included in new generation meningococcal vaccines, and establish proof-in-principle for clinical studies to compare their efficacy with wild-type fHbps.

Design and Evaluation of Meningococcal Vaccines through Structure-Based Modification of Host and Pathogen Molecules.,Johnson S, Tan L, van der Veen S, Caesar J, Goicoechea De Jorge E, Harding RJ, Bai X, Exley RM, Ward PN, Ruivo N, Trivedi K, Cumber E, Jones R, Newham L, Staunton D, Ufret-Vincenty R, Borrow R, Pickering MC, Lea SM, Tang CM PLoS Pathog. 2012 Oct;8(10):e1002981. doi: 10.1371/journal.ppat.1002981. Epub, 2012 Oct 25. PMID:23133374<ref>PMID:23133374</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2yby" style="background-color:#fffaf0;"></div>

==See Also==
*[[Complement factor 3D structures|Complement factor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Caesar JJE]]
[[Category: Everett RJ]]
[[Category: Johnson SJ]]
[[Category: Lea SM]]
[[Category: Tang CM]]