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[[Image:2ipu.jpg|left|200px]]
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{{STRUCTURE_2ipu|  PDB=2ipu  |  SCENE=  }}
'''PFA1 Fab fragment complexed with Abeta 1-8 peptide'''


==PFA1 Fab fragment complexed with Abeta 1-8 peptide==
<StructureSection load='2ipu' size='340' side='right'caption='[[2ipu]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ipu]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IPU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IPU 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]] 1.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACM:ACETAMIDE'>ACM</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=2ipu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ipu OCA], [https://pdbe.org/2ipu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ipu RCSB], [https://www.ebi.ac.uk/pdbsum/2ipu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ipu 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/ip/2ipu_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=2ipu ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Amyloid aggregates of the amyloid-beta (Abeta) peptide are implicated in the pathology of Alzheimer's disease. Anti-Abeta monoclonal antibodies (mAbs) have been shown to reduce amyloid plaques in vitro and in animal studies. Consequently, passive immunization is being considered for treating Alzheimer's, and anti-Abeta mAbs are now in phase II trials. We report the isolation of two mAbs (PFA1 and PFA2) that recognize Abeta monomers, protofibrils, and fibrils and the structures of their antigen binding fragments (Fabs) in complex with the Abeta(1-8) peptide DAEFRHDS. The immunodominant EFRHD sequence forms salt bridges, hydrogen bonds, and hydrophobic contacts, including interactions with a striking WWDDD motif of the antigen binding fragments. We also show that a similar sequence (AKFRHD) derived from the human protein GRIP1 is able to cross-react with both PFA1 and PFA2 and, when cocrystallized with PFA1, binds in an identical conformation to Abeta(1-8). Because such cross-reactivity has implications for potential side effects of immunotherapy, our structures provide a template for designing derivative mAbs that target Abeta with improved specificity and higher affinity.


==Overview==
Molecular basis for passive immunotherapy of Alzheimer's disease.,Gardberg AS, Dice LT, Ou S, Rich RL, Helmbrecht E, Ko J, Wetzel R, Myszka DG, Patterson PH, Dealwis C Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15659-64. Epub 2007 Sep 25. PMID:17895381<ref>PMID:17895381</ref>
Amyloid aggregates of the amyloid-beta (Abeta) peptide are implicated in the pathology of Alzheimer's disease. Anti-Abeta monoclonal antibodies (mAbs) have been shown to reduce amyloid plaques in vitro and in animal studies. Consequently, passive immunization is being considered for treating Alzheimer's, and anti-Abeta mAbs are now in phase II trials. We report the isolation of two mAbs (PFA1 and PFA2) that recognize Abeta monomers, protofibrils, and fibrils and the structures of their antigen binding fragments (Fabs) in complex with the Abeta(1-8) peptide DAEFRHDS. The immunodominant EFRHD sequence forms salt bridges, hydrogen bonds, and hydrophobic contacts, including interactions with a striking WWDDD motif of the antigen binding fragments. We also show that a similar sequence (AKFRHD) derived from the human protein GRIP1 is able to cross-react with both PFA1 and PFA2 and, when cocrystallized with PFA1, binds in an identical conformation to Abeta(1-8). Because such cross-reactivity has implications for potential side effects of immunotherapy, our structures provide a template for designing derivative mAbs that target Abeta with improved specificity and higher affinity.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IPU OCA].
</div>
<div class="pdbe-citations 2ipu" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Molecular basis for passive immunotherapy of Alzheimer's disease., Gardberg AS, Dice LT, Ou S, Rich RL, Helmbrecht E, Ko J, Wetzel R, Myszka DG, Patterson PH, Dealwis C, Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15659-64. Epub 2007 Sep 25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17895381 17895381]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
[[Category: Dealwis, C.]]
== References ==
[[Category: Gardberg, A S.]]
<references/>
[[Category: Abeta]]
__TOC__
[[Category: Cdr]]
</StructureSection>
[[Category: Immune system]]
[[Category: Homo sapiens]]
[[Category: Wwddd]]
[[Category: Large Structures]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 07:45:35 2008''
[[Category: Mus musculus]]
[[Category: Dealwis C]]
[[Category: Gardberg AS]]
Retrieved from "https://proteopedia.org/2ipu"