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| - | <table cellpadding='5'><tr><td style='background-color: yellow;border:2px solid black;font-size:150%;'> | + | <span style='background-color: yellow;'>For additional information see '''2009, December:''' at [[Retractions and Fraud]].</span></br>REMOVED: The PDB entry 2a01 was removed. |
| - | WARNING: This structure was flagged as problematic. For additional information see '''2009, December:''' at [[Retractions and Fraud]].</td></tr></table>
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| - | ==Crystal Structure of Lipid-free Human Apolipoprotein A-I==
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| - | <StructureSection load='2a01' size='340' side='right' caption='[[2a01]], [[Resolution|resolution]] 2.40Å' scene=''>
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| - | == Structural highlights ==
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| - | <table><tr><td colspan='2'>[[2a01]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A01 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2A01 FirstGlance]. <br>
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| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AC9:TRISACETYLACETONATOCHROMIUM(III)'>AC9</scene></td></tr>
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| - | <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=2a01 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a01 OCA], [http://pdbe.org/2a01 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2a01 RCSB], [http://www.ebi.ac.uk/pdbsum/2a01 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2a01 ProSAT]</span></td></tr>
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| - | </table>
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| - | == Disease ==
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| - | [[http://www.uniprot.org/uniprot/APOA1_HUMAN APOA1_HUMAN]] Defects in APOA1 are a cause of high density lipoprotein deficiency type 2 (HDLD2) [MIM:[http://omim.org/entry/604091 604091]]; also known as familial hypoalphalipoproteinemia (FHA). Inheritance is autosomal dominant.<ref>PMID:8240372</ref> <ref>PMID:8282791</ref> Defects in APOA1 are a cause of the low HDL levels observed in high density lipoprotein deficiency type 1 (HDLD1) [MIM:[http://omim.org/entry/205400 205400]]; also known as analphalipoproteinemia or Tangier disease (TGD). HDLD1 is a recessive disorder characterized by the absence of plasma HDL, accumulation of cholesteryl esters, premature coronary artery disease, hepatosplenomegaly, recurrent peripheral neuropathy and progressive muscle wasting and weakness. In HDLD1 patients, ApoA-I fails to associate with HDL probably because of the faulty conversion of pro-ApoA-I molecules into mature chains, either due to a defect in the converting enzyme activity or a specific structural defect in Tangier ApoA-I.<ref>PMID:8240372</ref> <ref>PMID:8282791</ref> Note=A mutation in APOA1 is the cause of amyloid polyneuropathy-nephropathy Iowa type (AMYLIOWA); also known as amyloidosis van Allen type or familial amyloid polyneuropathy type III. AMYLIOWA is a hereditary generalized amyloidosis due to deposition of amyloid mainly constituted by apolipoprotein A1. The clinical picture is dominated by neuropathy in the early stages of the disease and nephropathy late in the course. Death is due in most cases to renal amyloidosis. Severe peptic ulcer disease can occurr in some and hearing loss is frequent. Cataracts is present in several, but vitreous opacities are not observed.<ref>PMID:8240372</ref> <ref>PMID:8282791</ref> <ref>PMID:3142462</ref> <ref>PMID:2123470</ref> Defects in APOA1 are a cause of amyloidosis type 8 (AMYL8) [MIM:[http://omim.org/entry/105200 105200]]; also known as systemic non-neuropathic amyloidosis or Ostertag-type amyloidosis. AMYL8 is a hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash.<ref>PMID:8240372</ref> <ref>PMID:8282791</ref> <ref>PMID:1502149</ref>
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| - | == Function ==
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| - | [[http://www.uniprot.org/uniprot/APOA1_HUMAN APOA1_HUMAN]] Participates in the reverse transport of cholesterol from tissues to the liver for excretion by promoting cholesterol efflux from tissues and by acting as a cofactor for the lecithin cholesterol acyltransferase (LCAT). As part of the SPAP complex, activates spermatozoa motility.<ref>PMID:1909888</ref>
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| - | == Evolutionary Conservation ==
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| - | [[Image:Consurf_key_small.gif|200px|right]]
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| - | Check<jmol>
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| - | <jmolCheckbox>
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| - | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a0/2a01_consurf.spt"</scriptWhenChecked>
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| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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| - | <text>to colour the structure by Evolutionary Conservation</text>
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| - | </jmolCheckbox>
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| - | </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=2a01 ConSurf].
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| - | <div style="clear:both"></div>
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| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Despite three decades of extensive studies on human apolipoprotein A-I (apoA-I), the major protein component in high-density lipoproteins, the molecular basis for its antiatherogenic function is elusive, in part because of lack of a structure of the full-length protein. We describe here the crystal structure of lipid-free apoA-I at 2.4 A. The structure shows that apoA-I is comprised of an N-terminal four-helix bundle and two C-terminal helices. The N-terminal domain plays a prominent role in maintaining its lipid-free conformation, indicating that mutants with truncations in this region form inadequate models for explaining functional properties of apoA-I. A model for transformation of the lipid-free conformation to the high-density lipoprotein-bound form follows from an analysis of solvent-accessible hydrophobic patches on the surface of the structure and their proximity to the hydrophobic core of the four-helix bundle. The crystal structure of human apoA-I displays a hitherto-unobserved array of positively and negatively charged areas on the surface. Positioning of the charged surface patches relative to hydrophobic regions near the C terminus of the protein offers insights into its interaction with cell-surface components of the reverse cholesterol transport pathway and antiatherogenic properties of this protein. This structure provides a much-needed structural template for exploration of molecular mechanisms by which human apoA-I ameliorates atherosclerosis and inflammatory diseases.
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| - | Crystal structure of human apolipoprotein A-I: insights into its protective effect against cardiovascular diseases.,Ajees AA, Anantharamaiah GM, Mishra VK, Hussain MM, Murthy HM Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2126-31. Epub 2006 Feb 1. PMID:16452169<ref>PMID:16452169</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 2a01" style="background-color:#fffaf0;"></div>
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| - | ==See Also==
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| - | *[[Retractions and Fraud|Retractions and Fraud]]
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| - | == References ==
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| - | <references/>
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| - | __TOC__
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| - | </StructureSection>
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| - | [[Category: Human]]
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| - | [[Category: Ajees, A A]]
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| - | [[Category: Anantharamaiah, G M]]
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| - | [[Category: Hussain, M M]]
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| - | [[Category: Mishra, V K]]
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| - | [[Category: Murthy, K H.M]]
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| - | [[Category: Four-helix bundle]]
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| - | [[Category: Lipid transport]]
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