1mnu: Difference between revisions

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-[[Image:1mnu.gif|left|200px]]<br />
-<applet load="1mnu" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1mnu, resolution 2.5&Aring;" />
-'''UNLIGANDED BACTERICIDAL ANTIBODY AGAINST NEISSERIA MENINGITIDIS'''<br />
-==Overview==
+==UNLIGANDED BACTERICIDAL ANTIBODY AGAINST NEISSERIA MENINGITIDIS==
-MN12H2 is a bactericidal antibody directed against outer membrane protein, PorA epitope P1.16 of Neisseria meningitidis. Binding of MN12H2 to PorA at, the meningococcal surface activates the classical complement pathway, resulting in bacterial lysis. We have determined the crystal structure of, the unliganded MN12H2 Fab fragment in two different crystal forms and, compared it with the structure of the Fab in complex with a P1.16-derived, peptide. The unliganded Fabs have elbow bend angles of 155 degrees and 159, degrees, whereas the liganded Fab has a more closed elbow bend of 143, degrees. Substantial differences in quaternary and tertiary structure of, the antigen binding site are observed between the unliganded and liganded, MN12H2 Fab structures that can be attributed to peptide binding. The, variable light and heavy chain interface of the liganded Fab is twisted by, a 5 degrees rotation along an axis approximately perpendicular to the, plane of the interface. Hypervariable loops H1, H2, and framework loop, FR-H3 follow this rotation. The hypervariable loop H3 undergoes, conformational changes but remains closely linked to hypervariable loop, L1. In contrast with the binding site expansion seen in other Fab-peptide, structures, the MN12H2 binding site is narrowed upon peptide binding due, to the formation of a "false floor" mediated by arginine residue 101 of, the light chain. These results indicate that PorA epitope P1.16 of N., meningitidis is recognized by the complement-activating antibody MN12H2, through induced fit, allowing the formation of a highly complementary, immune complex.
+<StructureSection load='1mnu' size='340' side='right'caption='[[1mnu]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1mnu]] is a 2 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=1MNU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MNU 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]] 2.5&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</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=1mnu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mnu OCA], [https://pdbe.org/1mnu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mnu RCSB], [https://www.ebi.ac.uk/pdbsum/1mnu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mnu ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/A2NHM3_MOUSE A2NHM3_MOUSE]
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mn/1mnu_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1mnu ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+MN12H2 is a bactericidal antibody directed against outer membrane protein PorA epitope P1.16 of Neisseria meningitidis. Binding of MN12H2 to PorA at the meningococcal surface activates the classical complement pathway resulting in bacterial lysis. We have determined the crystal structure of the unliganded MN12H2 Fab fragment in two different crystal forms and compared it with the structure of the Fab in complex with a P1.16-derived peptide. The unliganded Fabs have elbow bend angles of 155 degrees and 159 degrees, whereas the liganded Fab has a more closed elbow bend of 143 degrees. Substantial differences in quaternary and tertiary structure of the antigen binding site are observed between the unliganded and liganded MN12H2 Fab structures that can be attributed to peptide binding. The variable light and heavy chain interface of the liganded Fab is twisted by a 5 degrees rotation along an axis approximately perpendicular to the plane of the interface. Hypervariable loops H1, H2, and framework loop FR-H3 follow this rotation. The hypervariable loop H3 undergoes conformational changes but remains closely linked to hypervariable loop L1. In contrast with the binding site expansion seen in other Fab-peptide structures, the MN12H2 binding site is narrowed upon peptide binding due to the formation of a "false floor" mediated by arginine residue 101 of the light chain. These results indicate that PorA epitope P1.16 of N. meningitidis is recognized by the complement-activating antibody MN12H2 through induced fit, allowing the formation of a highly complementary immune complex.
-==About this Structure==
+Bactericidal antibody recognition of meningococcal PorA by induced fit. Comparison of liganded and unliganded Fab structures.,van den Elsen J, Vandeputte-Rutten L, Kroon J, Gros P J Biol Chem. 1999 Jan 15;274(3):1495-501. PMID:9880525<ref>PMID:9880525</ref>
-MNU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with CD as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1MNU OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-Bactericidal antibody recognition of meningococcal PorA by induced fit. Comparison of liganded and unliganded Fab structures., van den Elsen J, Vandeputte-Rutten L, Kroon J, Gros P, J Biol Chem. 1999 Jan 15;274(3):1495-501. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9880525 9880525]
+</div>
+<div class="pdbe-citations 1mnu" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Antibody 3D structures|Antibody 3D structures]]
+*[[Sandbox 20009|Sandbox 20009]]
+*[[3D structures of non-human antibody|3D structures of non-human antibody]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Protein complex]]
+[[Category: Gros P]]
-[[Category: Elsen, J.Van.Den.]]
+[[Category: Kroon J]]
-[[Category: Gros, P.]]
+[[Category: Van Den Elsen J]]
-[[Category: Kroon, J.]]
+[[Category: Vandeputte-Rutten L]]
-[[Category: Vandeputte-Rutten, L.]]
-[[Category: CD]]
-[[Category: bactericidal antibody]]
-[[Category: epitope p1.16 of pora from neisseria meningitidis]]
-[[Category: murine immunoglobulin igg2a kappa]]
-[[Category: unliganded]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 18 09:37:09 2007''