View source for 3eob


==Crystal structure the Fab fragment of Efalizumab in complex with LFA-1 I domain, Form II==
<StructureSection load='3eob' size='340' side='right'caption='[[3eob]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3eob]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EOB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EOB 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]] 3.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=3eob FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eob OCA], [https://pdbe.org/3eob PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3eob RCSB], [https://www.ebi.ac.uk/pdbsum/3eob PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3eob ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ITAL_HUMAN ITAL_HUMAN] Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. It is involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated killing, and antibody dependent killing by granulocytes and monocytes.
== 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/eo/3eob_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=3eob ConSurf].
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== Publication Abstract from PubMed ==
Lymphocyte function-associated antigen 1 (LFA-1) plays important roles in immune cell adhesion, trafficking, and activation and is a therapeutic target for the treatment of multiple autoimmune diseases. Efalizumab is one of the most efficacious antibody drugs for treating psoriasis, a very common skin disease, through inhibition of the binding of LFA-1 to the ligand intercellular adhesion molecule 1 (ICAM-1). We report here the crystal structures of the Efalizumab Fab alone and in complex with the LFA-1 alpha(L) I domain, which reveal the molecular mechanism of inhibition of LFA-1 by Efalizumab. The Fab binds with an epitope on the inserted (I) domain that is distinct from the ligand-binding site. Efalizumab binding blocks the binding of LFA-1 to ICAM-1 via steric hindrance between its light chain and ICAM-1 domain 2 and thus inhibits the activities of LFA-1. These results have important implications for the development of improved antibodies and new therapeutic strategies for the treatment of autoimmune diseases.

Efalizumab binding to the LFA-1 alphaL I domain blocks ICAM-1 binding via steric hindrance.,Li S, Wang H, Peng B, Zhang M, Zhang D, Hou S, Guo Y, Ding J Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4349-54. Epub 2009 Mar 3. PMID:19258452<ref>PMID:19258452</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Integrin 3D structures|Integrin 3D structures]]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ding J]]
[[Category: Li S]]