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==Crystal Structure of the 22kDa N-Terminal Fragment of Mouse Apolipoprotein E==
==Crystal Structure of the 22kDa N-Terminal Fragment of Mouse Apolipoprotein E==
<StructureSection load='1ya9' size='340' side='right' caption='[[1ya9]], [[Resolution|resolution]] 2.09&Aring;' scene=''>
<StructureSection load='1ya9' size='340' side='right'caption='[[1ya9]], [[Resolution|resolution]] 2.09&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1ya9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YA9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1YA9 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1ya9]] is a 1 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=1YA9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YA9 FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Apoe ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.09&#8491;</td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ya9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ya9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ya9 RCSB], [http://www.ebi.ac.uk/pdbsum/1ya9 PDBsum]</span></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=1ya9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ya9 OCA], [https://pdbe.org/1ya9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ya9 RCSB], [https://www.ebi.ac.uk/pdbsum/1ya9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ya9 ProSAT]</span></td></tr>
<table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/APOE_MOUSE APOE_MOUSE] Mediates the binding, internalization, and catabolism of lipoprotein particles. It can serve as a ligand for the LDL (apo B/E) receptor and for the specific apo-E receptor (chylomicron remnant) of hepatic tissues.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ya/1ya9_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ya/1ya9_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </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/chain_selection.php?pdb_ID=2ata ConSurf].
</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=1ya9 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Apolipoprotein (apo) E4 is a major risk factor for Alzheimer and cardiovascular diseases. ApoE4 differs from the two other common isoforms (apoE2 and apoE3) by its lower resistance to denaturation and greater propensity to form partially folded intermediates. As a first step to determine the importance of stability differences in vivo, we reengineered a partially humanized variant of the amino-terminal domain of mouse apoE (T61R mouse apoE) to acquire a destabilized conformation like that of apoE4. For this process, we determined the crystal structure of wild-type mouse apoE, which, like apoE4, forms a four-helix bundle, and identified two structural differences in the turn between helices 2 and 3 and in the middle of helix 3 as potentially destabilizing sites. Introducing mutations G83T and N113G at these sites destabilized the mouse apoE conformation. The mutant mouse apoE more rapidly remodeled phospholipid than T61R mouse apoE, which supports the hypothesis that a destabilized conformation promotes apoE4 lipid binding.
Engineering conformational destabilization into mouse apolipoprotein E. A model for a unique property of human apolipoprotein E4.,Hatters DM, Peters-Libeu CA, Weisgraber KH J Biol Chem. 2005 Jul 15;280(28):26477-82. Epub 2005 May 11. PMID:15890642<ref>PMID:15890642</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Hatters, D M.]]
[[Category: Hatters DM]]
[[Category: Newhouse, Y.]]
[[Category: Newhouse Y]]
[[Category: Peters-Libeu, C A.]]
[[Category: Peters-Libeu CA]]
[[Category: Rutenber, E.]]
[[Category: Rutenber E]]
[[Category: Weisgraber, K H.]]
[[Category: Weisgraber KH]]
[[Category: Apolipoprotein e]]
[[Category: Ldl receptor binding]]
[[Category: Lipid transport]]
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