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New page: left|200px<br /> <applet load="1ajj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ajj, resolution 1.7Å" /> '''LDL RECEPTOR LIGAND-...
 
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[[Image:1ajj.gif|left|200px]]<br />
<applet load="1ajj" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1ajj, resolution 1.7&Aring;" />
'''LDL RECEPTOR LIGAND-BINDING MODULE 5, CALCIUM-COORDINATING'''<br />


==Overview==
==LDL RECEPTOR LIGAND-BINDING MODULE 5, CALCIUM-COORDINATING==
The low-density lipoprotein receptor (LDLR) is responsible for the uptake, of cholesterol-containing lipoprotein particles into cells. The, amino-terminal region of LDLR, which consists of seven tandemly repeated, approximately 40-amino-acid, cysteine-rich modules (LDL-A modules), mediates binding to lipoproteins. LDL-A modules are biologically, ubiquitous domains, found in over 100 proteins in the sequence database., The structure of ligand-binding repeat 5 (LR5) of the LDLR, determined to, 1.7 A resolution by X-ray crystallography and presented here, contains a, calcium ion coordinated by acidic residues that lie at the, carboxy-terminal end of the domain and are conserved among LDL-A modules., Naturally occurring point mutations found in patients with the disease, familial hypercholesterolaemia alter residues that directly coordinate, Ca2+ or that serve as scaffolding residues of LR5.
<StructureSection load='1ajj' size='340' side='right'caption='[[1ajj]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ajj]] is a 1 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=1AJJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AJJ 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]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1ajj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ajj OCA], [https://pdbe.org/1ajj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ajj RCSB], [https://www.ebi.ac.uk/pdbsum/1ajj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ajj ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/LDLR_HUMAN LDLR_HUMAN] Defects in LDLR are the cause of familial hypercholesterolemia (FH) [MIM:[https://omim.org/entry/143890 143890]; a common autosomal semi-dominant disease that affects about 1 in 500 individuals. The receptor defect impairs the catabolism of LDL, and the resultant elevation in plasma LDL-cholesterol promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and coronary arteries (atherosclerosis).<ref>PMID:3263645</ref> <ref>PMID:2569482</ref> <ref>PMID:3955657</ref> <ref>PMID:8347689</ref> <ref>PMID:2318961</ref> <ref>PMID:1446662</ref> <ref>PMID:1867200</ref> <ref>PMID:8462973</ref> <ref>PMID:8168830</ref> <ref>PMID:2726768</ref> <ref>PMID:1464748</ref> <ref>PMID:7573037</ref> <ref>PMID:7583548</ref> <ref>PMID:7550239</ref> <ref>PMID:7635461</ref> <ref>PMID:7635482</ref> <ref>PMID:7649546</ref> <ref>PMID:7649549</ref> <ref>PMID:8740918</ref> <ref>PMID:8664907</ref> <ref>PMID:9026534</ref> <ref>PMID:9254862</ref> <ref>PMID:9143924</ref> <ref>PMID:9259195</ref> <ref>PMID:9104431</ref> <ref>PMID:9654205</ref> <ref>PMID:9452094</ref> <ref>PMID:9452095</ref> <ref>PMID:9452118</ref> <ref>PMID:10206683</ref> <ref>PMID:10660340</ref> [:]<ref>PMID:9852677</ref> <ref>PMID:9678702</ref> <ref>PMID:10422803</ref> <ref>PMID:10090484</ref> <ref>PMID:10447263</ref> <ref>PMID:10978268</ref> <ref>PMID:10980548</ref> <ref>PMID:10882754</ref> <ref>PMID:11298688</ref> <ref>PMID:17142622</ref> <ref>PMID:19319977</ref> <ref>PMID:22160468</ref>
== Function ==
[https://www.uniprot.org/uniprot/LDLR_HUMAN LDLR_HUMAN] Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. In case of HIV-1 infection, functions as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells.
== 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/aj/1ajj_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=1ajj ConSurf].
<div style="clear:both"></div>


==Disease==
==See Also==
Known disease associated with this structure: Hypercholesterolemia, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606945 606945]]
*[[LDL receptor|LDL receptor]]
 
== References ==
==About this Structure==
<references/>
1AJJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 and CA as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1AJJ OCA].
__TOC__
 
</StructureSection>
==Reference==
Molecular basis of familial hypercholesterolaemia from structure of LDL receptor module., Fass D, Blacklow S, Kim PS, Berger JM, Nature. 1997 Aug 14;388(6643):691-3. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9262405 9262405]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Berger, J.M.]]
[[Category: Berger JM]]
[[Category: Blacklow, S.C.]]
[[Category: Blacklow SC]]
[[Category: Fass, D.]]
[[Category: Fass D]]
[[Category: Kim, P.S.]]
[[Category: Kim PS]]
[[Category: CA]]
[[Category: SO4]]
[[Category: calcium]]
[[Category: cysteine-rich module]]
[[Category: ldl receptor]]
[[Category: receptor]]
 
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Retrieved from "https://proteopedia.org/1ajj"