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3eob
From Proteopedia
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| - | [[Image:3eob.png|left|200px]] | ||
| - | + | ==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]] 3.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3eob]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. 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='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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3eo9|3eo9]], [[3eoa|3eoa]]</div></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGG1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), LFA-1 I domain ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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/initialview01.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]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 3eob" style="background-color:#fffaf0;"></div> | |
| - | + | ||
==See Also== | ==See Also== | ||
| - | *[[Monoclonal | + | *[[Integrin 3D structures|Integrin 3D structures]] |
| - | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |
| - | == | + | == References == |
| - | < | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: Ding, J | + | </StructureSection> |
| - | [[Category: Li, S | + | [[Category: Human]] |
| + | [[Category: Large Structures]] | ||
| + | [[Category: Ding, J]] | ||
| + | [[Category: Li, S]] | ||
| + | [[Category: Alternative splicing]] | ||
[[Category: Antibody]] | [[Category: Antibody]] | ||
| + | [[Category: Calcium]] | ||
[[Category: Cd11a]] | [[Category: Cd11a]] | ||
[[Category: Cell adhesion]] | [[Category: Cell adhesion]] | ||
| Line 30: | Line 56: | ||
[[Category: Magnesium]] | [[Category: Magnesium]] | ||
[[Category: Membrane]] | [[Category: Membrane]] | ||
| + | [[Category: Polymorphism]] | ||
[[Category: Receptor]] | [[Category: Receptor]] | ||
[[Category: Transmembrane]] | [[Category: Transmembrane]] | ||
Current revision
Crystal structure the Fab fragment of Efalizumab in complex with LFA-1 I domain, Form II
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Categories: Human | Large Structures | Ding, J | Li, S | Alternative splicing | Antibody | Calcium | Cd11a | Cell adhesion | Efalizumab | Fab | Glycoprotein | I domain | Immune system-cell adhesion complex | Integrin | Lfa-1 | Magnesium | Membrane | Polymorphism | Receptor | Transmembrane

