1wej

From Proteopedia

(Difference between revisions)

Revision as of 16:45, 11 April 2018

IGG1 FAB FRAGMENT (OF E8 ANTIBODY) COMPLEXED WITH HORSE CYTOCHROME C AT 1.8 A RESOLUTION

Structural highlights

1wej is a 3 chain structure with sequence from Equus caballus and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CYC_HORSE] Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain. Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

A complete understanding of antibody-antigen association and specificity requires the stereochemical description of both antigen and antibody before and upon complex formation. The structural mechanism involved in the binding of the IgG1 monoclonal antibody E8 to its highly charged protein antigen horse cytochrome c (cyt c) is revealed by crystallographic structures of the antigen-binding fragment (Fab) of E8 bound to cyt c (FabE8-cytc), determined to 1.8 A resolution, and of uncomplexed Fab E8 (FabE8), determined to 2.26 A resolution. E8 antibody binds to three major discontiguous segments (33 to 39; 56 to 66; 96 to 104), and two minor sites on cyt c opposite to the exposed haem edge. Crystallographic definition of the E8 epitope complements and extends biochemical mapping and two-dimensional nuclear magnetic resonance with hydrogen-deuterium exchange studies. These combined results demonstrate that antibody-induced stabilization of secondary structural elements within the antigen can propagate locally to adjacent residues outside the epitope. Pre-existing shape complementarity at the FabE8-cytc interface is enhanced by 48 bound water molecules, and by local movements of up to 4.2 A for E8 antibody and 8.9 A for cyt c. Glu62, Asn103 and the C-terminal Glu104 of cyt c adjust to fit the pre-formed VL "hill" and VH "valley" shape of the grooved E8 paratope. All six E8 complementarity determining regions (CDRs) contact the antigen, with CDR L1 forming 46% of the total atomic contacts, and CDRs L1 (29%) and H3 (20%) contributing the highest percentage of the total surface area of E8 buried by cyt c (550 A2). The E8 antibody covers 534 A2 of the cyt c surface. The formation of five ion pairs between E8 and flexible cyt c residues Lys60, Glu62 and Glu104 suggests the importance of mobile regions and electrostatic interactions in providing the exquisite specificity needed for recognition of this extremely conserved protein antigen. The highly homologous VL domains of E8 and anti-lysozyme antibody D1. 3 achieve their distinct antigen-binding specificities by expanding the impact of their limited sequence differences through the recruitment of different sets of conserved residues and distinctly different CDR L3 conformations.

Structural basis for the binding of an anti-cytochrome c antibody to its antigen: crystal structures of FabE8-cytochrome c complex to 1.8 A resolution and FabE8 to 2.26 A resolution.,Mylvaganam SE, Paterson Y, Getzoff ED J Mol Biol. 1998 Aug 14;281(2):301-22. PMID:9698550^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mylvaganam SE, Paterson Y, Getzoff ED. Structural basis for the binding of an anti-cytochrome c antibody to its antigen: crystal structures of FabE8-cytochrome c complex to 1.8 A resolution and FabE8 to 2.26 A resolution. J Mol Biol. 1998 Aug 14;281(2):301-22. PMID:9698550 doi:10.1006/jmbi.1998.1942

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1wej"

@@ Line 1: / Line 1: @@
 ==IGG1 FAB FRAGMENT (OF E8 ANTIBODY) COMPLEXED WITH HORSE CYTOCHROME C AT 1.8 A RESOLUTION==
 <StructureSection load='1wej' size='340' side='right' caption='[[1wej]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></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=1wej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wej OCA], [http://pdbe.org/1wej PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wej RCSB], [http://www.ebi.ac.uk/pdbsum/1wej PDBsum]</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=1wej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wej OCA], [http://pdbe.org/1wej PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wej RCSB], [http://www.ebi.ac.uk/pdbsum/1wej PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1wej ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 13: / Line 14: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/we/1wej_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/we/1wej_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 31: / Line 32: @@
 ==See Also==
 *[[Cytochrome c|Cytochrome c]]
-*[[Monoclonal Antibody|Monoclonal Antibody]]
+*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
 == References ==
 <references/>

1wej

From Proteopedia

Revision as of 16:45, 11 April 2018

IGG1 FAB FRAGMENT (OF E8 ANTIBODY) COMPLEXED WITH HORSE CYTOCHROME C AT 1.8 A RESOLUTION

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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