LDL receptor

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<StructureSection load='2w2m' size='350' side='right' caption='Structure of human LDLR EGF precursor homology domain (magenta) complex with proprotein convertase subtilisin/kexin 9-CoA reductase (grey and green) and Ca+2 ions (PDB entry [[2w2m]])' scene=''>
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<StructureSection load='' size='350' side='right' caption='Structure of human LDLR LBD and EGFP domains (magenta) complex with proprotein convertase subtilisin/kexin 9-CoA reductase (cyan and green) and Ca+2 ions (green) (PDB entry [[3m0c]])' scene='54/545853/Cv/1'>
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== Function ==
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'''LDL (Low Density Lipoprotein) receptor''' (LDLR) mediates the endocytosis of cholesterol-rich LDL. LDLR recognizes the apoprotein B100 which is embedded in the outer layer of the LDL particle. LDLR sits on the cell surface and binds LDL particles which circulate in the blood stream. LDLR transports the LDL particle into the cell where the cholesterol is used. Upon release of the LDL particle, the LDLR is recycled back into the cell membrane surface<ref>PMID:19299327</ref>.
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'''LDL receptor''' (LDLR) mediates the endocytosis of cholesterol-rich LDL. LDLR recognizes the apoprotein B100 which is embedded in the outer layer of the LDL particle. LDLR consist of a ligand-binding domain (LBD residues 1-292), epidermal growth factor precursor homology domain (EGFP residues 293-699), oligosaccharide-rich domain (residues 700-758), membrane-spanning domain (residues 759-781) and cytoplasmic domain (residues 782-832). LDLR LBD contains 7 ca. 40 amino acid long repeats (LB) containing 6 cysteine residues, making a calcium binding octahedral structure. LDLR EGFP contains 2 EGF repeats followed by 6 YWTD repeats and another EGF repeat. LDLR LBD residues 133-273 are named C-type lectin-like domain. LDLR sits on the cell surface and binds LDL particles which circulate in the blood stream. LDLR transports the LDL particle into the cell where the cholesterol is used. Upon release of the LDL particle, the LDLR is recycled back into the cell membrane surface.
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See also [[Transmembrane (cell surface) receptors]]
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== Disease ==
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Mutations in LDLR which cause its lack of function are causing familial hypercholesterolemia<ref>PMID:9763532</ref>.
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== Structural highlights ==
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<scene name='54/545853/Cv/6'>LDLR complex with proprotein convertase subtilisin/kexin 9-CoA reductase and Ca+2 ions</scene>.
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<scene name='54/545853/Cv/7'>Ligand-binding domain (LBD) and epidermal growth factor precursor homology domain (EGFP) of LDLR</scene>.
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LDLR consists of a ligand-binding domain (LBD residues 1-292), epidermal growth factor precursor homology domain (EGFP residues 293-699), oligosaccharide-rich domain (residues 700-758), membrane-spanning domain (residues 759-781) and cytoplasmic domain (residues 782-832). LDLR LBD contains 7 ca. 40 amino acid long repeats (LB1 residues 20-67; LB2 residues 55-104; LB3 residues 105-143; LB4 residues 144-196; LB5 residues 196-232; LB6 residues 234-272) containing 6 cysteine residues, making a calcium binding octahedral structure. LDLR EGFP contains 2 EGF repeats followed by 6 <scene name='54/545853/Cv/8'>YWTD repeats</scene> and another EGF repeat. LDLR LBD residues 133-273 are named C-type lectin-like domain.
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</StructureSection>
==3D structures of LDL receptor==
==3D structures of LDL receptor==
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*hLDLR ligand-binding domain;Repeats - LB1 20-67; LB2 55-104; LB4 144-195; LB5 196-232; LB6 234-272; LB7 274-313
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**[[1ldl]] – hLDLR LB1 - human - NMR<br />
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**[[1ldr]] – hLDLR LB2 - NMR<br />
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**[[1ajj]] – hLDLR LB5<br />
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**[[1d2j]], [[1f8z]] – hLDLR LB6 - NMR<br />
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**[[1f5y]] – hLDLR LB1,LB2 - NMR<br />
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**[[2lgp]] – hLDLR LB4,LB5 - NMR<br />
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**[[1xfe]] – hLDLR LB7,EGF - NMR<br />
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**[[1yxj]], [[1yxk]], [[6tl7]], [[6tla]] – hLDLR LBD LB4,LB5,LB6<br />
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**[[6tl9]] – hLDLR LBD LB4,LB5,LB6 + inhibitor<br />
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*hLDLR ligand-binding domain complex with protein
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===hLDLR LBD===
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**[[2fcw]] – hLDLR LB3,LB4 + α-2-macroglobulin receptor-associated protein<br />
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**[[2kri]] – hLDLR LB4 + β-2-glycoprotein - NMR<br />
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**[[5oyl]] – hLDLR LBD LB2 + glycoprotein <br />
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**[[5oy9]] – hLDLR LBD LB3 + glycoprotein G<br />
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[[1ldl]] – hLDLR LBD LB1 - human - NMR<br />
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*hLDLR EGFP domain 263-699
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[[1ldr]] – hLDLR LBD LB2 - NMR<br />
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[[1ajj]] – hLDLR LBD LB5<br />
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[[1d2j]], [[1f8z]] – hLDLR LBD LB6 - NMR<br />
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[[1f5y]] – hLDLR LBD LB1,LB2 - NMR<br />
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[[2lgp]] – hLDLR LBD LB4,LB5 - NMR<br />
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[[1xfe]] – hLDLR LBD LB7,EGF - NMR<br />
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===hLDLR LBD complex with protein===
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**[[1ijq]] – hLDLR YWTD-EGF<br />
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**[[1hj7]] – hLDLR EGF-EGF - NMR<br />
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**[[1hz8]], [[1i0u]] – hLDLR EGF1, EGF2 - NMR<br />
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**[[2mg9]] – hLDLR EGF1 - NMR<br />
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**[[4ne9]] – hLDLR EGF1 + PCSK9<br />
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[[2fcw]] – hLDLR LBD LB3,LB4 + α-2-macroglobulin receptor-associated protein<br />
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*hLDLR EGFP complex with protein
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[[2kri]] – hLDLR LBD LB4 + β-2-glycoprotein - NMR<br />
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===hLDLR EGFP===
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**[[3bps]], [[2w2m]], [[2w2o]], [[2w2p]], [[2w2q]], [[3gcx]] – hLDLR EGF1, EGF2 + proprotein convertase subtilisin/kexin 9<br />
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**[[2w2n]], [[3gcw]] – hLDLR EGF1, EGF2 (mutant) + proprotein convertase subtilisin/kexin 9<br />
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[[1ijq]] – hLDLR YWTD-EGF<br />
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*hLDLR cytoplasmic domain C terminal 817-832
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[[1hj7]] – hLDLR EGF-EGF - NMR<br />
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[[1hz8]], [[1i0u]] – hLDLR EGF1, EGF2 - NMR<br />
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===hLDLR EGFP complex with protein===
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**[[3so6]] – hLDLR C terminal + LDLR adaptor protein<br />
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[[3bps]], [[2w2m]], [[2w2o]], [[2w2p]], [[2w2q]], [[3gcx]] – hLDLR EGF1, EGF2 + proprotein convertase subtilisin/kexin 9<br />
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*hLDLR lectin-like domain 136-273
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[[2w2n]], [[3gcw]] – hLDLR EGF1, EGF2 (mutant) + proprotein convertase subtilisin/kexin 9<br />
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===hLDLR cytoplasmic domain===
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**[[1ypo]], [[1ypq]], [[1ypu]], [[7w5d]], [[7xmp]] – hLDLR<br />
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**[[3vlg]] – hLDLR (mutant)<br />
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[[3so6]] – hLDLR cytoplasmic domain C terminal + LDLR adaptor protein<br />
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*hLDLR Cys-rich domain 70-190
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===hLDLR lectin-like domain===
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**[[6byv]] – hLDLR - NMR<br />
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[[3vlg]] – hLDLR (mutant)<br />
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*hLDLR multiple domains
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===hLDLR several domains===
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**[[1n7d]] – hLDLR LBD,EGFP domains<br />
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**[[3m0c]] – hLDLR LBD,EGFP, oligosaccharide-rich, membrane-spanning domains + proprotein convertase subtilisin/kexin 9<br />
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**[[3p5b]], [[3p5c]] – hLDLR EGFP, oligosaccharide-rich, domains + proprotein convertase subtilisin/kexin 9<br />
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**[[9bdt]], [[9coo]] – hLDLR + apolipoprotein B + legobody + nanobody + MBP – Cryo EM<br />
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**[[9bd8]], [[9bde]] – hLDLR + apolipoprotein B – Cryo EM<br />
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[[1n7d]] – hLDLR LBD,EGFP domains<br />
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}}
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[[3m0c]] – hLDLR LBD,EGFP, oligosaccharide-rich, membrane-spanning domains + proprotein convertase subtilisin/kexin 9<br />
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== References ==
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[[3p5b]], [[3p5c]] – hLDLR EGFP, oligosaccharide-rich, domains + proprotein convertase subtilisin/kexin 9<br />
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<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Structure of human LDLR LBD and EGFP domains (magenta) complex with proprotein convertase subtilisin/kexin 9-CoA reductase (cyan and green) and Ca+2 ions (green) (PDB entry 3m0c)

Drag the structure with the mouse to rotate

3D structures of LDL receptor

Updated on 26-October-2025

References

  1. ↑ Goldstein JL, Brown MS. The LDL receptor. Arterioscler Thromb Vasc Biol. 2009 Apr;29(4):431-8. doi:, 10.1161/ATVBAHA.108.179564. PMID:19299327 doi:http://dx.doi.org/10.1161/ATVBAHA.108.179564
  2. ↑ Mak YT, Pang CP, Tomlinson B, Zhang J, Chan YS, Mak TW, Masarei JR. Mutations in the low-density lipoprotein receptor gene in Chinese familial hypercholesterolemia patients. Arterioscler Thromb Vasc Biol. 1998 Oct;18(10):1600-5. PMID:9763532

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Michal Harel, Alexander Berchansky, Joel L. Sussman

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