1f5y

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NMR STRUCTURE OF A CONCATEMER OF THE FIRST AND SECOND LIGAND-BINDING MODULES OF THE HUMAN LDL RECEPTOR

Structural highlights

1f5y is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 20 models
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

LDLR_HUMAN Defects in LDLR are the cause of familial hypercholesterolemia (FH) [MIM: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).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14] ^[15] ^[16] ^[17] ^[18] ^[19] ^[20] ^[21] ^[22] ^[23] ^[24] ^[25] ^[26] ^[27] ^[28] ^[29] ^[30] ^[31] [:]^[32] ^[33] ^[34] ^[35] ^[36] ^[37] ^[38] ^[39] ^[40] ^[41] ^[42] ^[43]

Function

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

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The ligand-binding domain of the human low-density lipoprotein receptor consists of seven modules, each of 40-45 residues. In the presence of calcium, these modules adopt a common polypeptide fold with three conserved disulfide bonds. A concatemer of the first and second modules (LB(1-2)) folds efficiently in the presence of calcium ions, forming the same disulfide connectivities as in the isolated modules. The three-dimensional structure of LB(1-2) has now been solved using two-dimensional 1H NMR spectroscopy and restrained molecular dynamics calculations. No intermodule nuclear Overhauser effects were observed, indicating the absence of persistent interaction between them. The near random-coil NH and H alpha chemical shifts and the low phi and psi angle order parameters of the four-residue linker suggest that it has considerable flexibility. The family of LB(1-2) structures superimposed well over LB1 or LB2, but not over both modules simultaneously. LB1 and LB2 have a similar pattern of calcium ligands, but the orientations of the indole rings of the tryptophan residues W23 and W66 differ, with the latter limiting solvent access to the calcium ion. From these studies, it appears that although most of the modules in the ligand-binding region of the receptor are joined by short segments, these linkers may impart considerable flexibility on this region.

NMR structure of a concatemer of the first and second ligand-binding modules of the human low-density lipoprotein receptor.,Kurniawan ND, Atkins AR, Bieri S, Brown CJ, Brereton IM, Kroon PA, Smith R Protein Sci. 2000 Jul;9(7):1282-93. PMID:10933493^[44]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Leitersdorf E, Hobbs HH, Fourie AM, Jacobs M, van der Westhuyzen DR, Coetzee GA. Deletion in the first cysteine-rich repeat of low density lipoprotein receptor impairs its transport but not lipoprotein binding in fibroblasts from a subject with familial hypercholesterolemia. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7912-6. PMID:3263645
↑ Leitersdorf E, Van der Westhuyzen DR, Coetzee GA, Hobbs HH. Two common low density lipoprotein receptor gene mutations cause familial hypercholesterolemia in Afrikaners. J Clin Invest. 1989 Sep;84(3):954-61. PMID:2569482 doi:http://dx.doi.org/10.1172/JCI114258
↑ Davis CG, Lehrman MA, Russell DW, Anderson RG, Brown MS, Goldstein JL. The J.D. mutation in familial hypercholesterolemia: amino acid substitution in cytoplasmic domain impedes internalization of LDL receptors. Cell. 1986 Apr 11;45(1):15-24. PMID:3955657
↑ Rubinsztein DC, Jialal I, Leitersdorf E, Coetzee GA, van der Westhuyzen DR. Identification of two new LDL-receptor mutations causing homozygous familial hypercholesterolemia in a South African of Indian origin. Biochim Biophys Acta. 1993 Aug 4;1182(1):75-82. PMID:8347689
↑ Leitersdorf E, Tobin EJ, Davignon J, Hobbs HH. Common low-density lipoprotein receptor mutations in the French Canadian population. J Clin Invest. 1990 Apr;85(4):1014-23. PMID:2318961 doi:http://dx.doi.org/10.1172/JCI114531
↑ Miyake Y, Tajima S, Funahashi T, Yamamura T, Yamamoto A. A point mutation of low-density-lipoprotein receptor causing rapid degradation of the receptor. Eur J Biochem. 1992 Nov 15;210(1):1-7. PMID:1446662
↑ Meiner V, Landsberger D, Berkman N, Reshef A, Segal P, Seftel HC, van der Westhuyzen DR, Jeenah MS, Coetzee GA, Leitersdorf E. A common Lithuanian mutation causing familial hypercholesterolemia in Ashkenazi Jews. Am J Hum Genet. 1991 Aug;49(2):443-9. PMID:1867200
↑ Leitersdorf E, Reshef A, Meiner V, Dann EJ, Beigel Y, van Roggen FG, van der Westhuyzen DR, Coetzee GA. A missense mutation in the low density lipoprotein receptor gene causes familial hypercholesterolemia in Sephardic Jews. Hum Genet. 1993 Mar;91(2):141-7. PMID:8462973
↑ Lelli N, Garuti R, Pedrazzi P, Ghisellini M, Simone ML, Tiozzo R, Cattin L, Valenti M, Rolleri M, Bertolini S, et al.. A new missense mutation (Cys297-->Phe) of the low density lipoprotein receptor in Italian patients with familial hypercholesterolemia (FHTrieste). Hum Genet. 1994 May;93(5):538-40. PMID:8168830
↑ Soutar AK, Knight BL, Patel DD. Identification of a point mutation in growth factor repeat C of the low density lipoprotein-receptor gene in a patient with homozygous familial hypercholesterolemia that affects ligand binding and intracellular movement of receptors. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4166-70. PMID:2726768
↑ Rubinsztein DC, Coetzee GA, Marais AD, Leitersdorf E, Seftel HC, van der Westhuyzen DR. Identification and properties of the proline664-leucine mutant LDL receptor in South Africans of Indian origin. J Lipid Res. 1992 Nov;33(11):1647-55. PMID:1464748
↑ Koivisto UM, Viikari JS, Kontula K. Molecular characterization of minor gene rearrangements in Finnish patients with heterozygous familial hypercholesterolemia: identification of two common missense mutations (Gly823-->Asp and Leu380-->His) and eight rare mutations of the LDL receptor gene. Am J Hum Genet. 1995 Oct;57(4):789-97. PMID:7573037
↑ Maruyama T, Miyake Y, Tajima S, Harada-Shiba M, Yamamura T, Tsushima M, Kishino B, Horiguchi Y, Funahashi T, Matsuzawa Y, et al.. Common mutations in the low-density-lipoprotein-receptor gene causing familial hypercholesterolemia in the Japanese population. Arterioscler Thromb Vasc Biol. 1995 Oct;15(10):1713-8. PMID:7583548
↑ Tricot-Guerber F, Saint-Jore B, Valenti K, Foulon T, Bost M, Hadjian AJ. Identification of a mutation, N543H, in exon 11 of the low-density lipoprotein receptor gene in a French family with familial hypercholesterolemia. Hum Mutat. 1995;6(1):87-8. PMID:7550239 doi:http://dx.doi.org/10.1002/humu.1380060117
↑ Ekstrom U, Abrahamson M, Sveger T, Lombardi P, Nilsson-Ehle P. An efficient screening procedure detecting six novel mutations in the LDL receptor gene in Swedish children with hypercholesterolemia. Hum Genet. 1995 Aug;96(2):147-50. PMID:7635461
↑ Leren TP, Solberg K, Rodningen OK, Tonstad S, Ose L. Two novel point mutations in the EGF precursor homology domain of the LDL receptor gene causing familial hypercholesterolemia. Hum Genet. 1995 Aug;96(2):241-2. PMID:7635482
↑ Giesel J, Holzem G, Oette K. Screening for mutations in exon 4 of the LDL receptor gene in a German population with severe hypercholesterolemia. Hum Genet. 1995 Sep;96(3):301-4. PMID:7649546
↑ Pereira E, Ferreira R, Hermelin B, Thomas G, Bernard C, Bertrand V, Nassiff H, Mendez del Castillo D, Bereziat G, Benlian P. Recurrent and novel LDL receptor gene mutations causing heterozygous familial hypercholesterolemia in La Habana. Hum Genet. 1995 Sep;96(3):319-22. PMID:7649549
↑ Gundersen KE, Solberg K, Rodningen OK, Tonstad S, Ose L, Berg K, Leren TP. Two novel missense mutations in the LDL receptor gene causing familial hypercholesterolemia. Clin Genet. 1996 Feb;49(2):85-7. PMID:8740918
↑ Sundvold H, Solberg K, Tonstad S, Rodningen OK, Ose L, Berg K, Leren TP. A common missense mutation (C210G) in the LDL receptor gene among Norwegian familial hypercholesterolemia subjects. Hum Mutat. 1996;7(1):70-1. PMID:8664907 doi:<70::AID-HUMU12>3.0.CO;2-P 10.1002/(SICI)1098-1004(1996)7:1<70::AID-HUMU12>3.0.CO;2-P
↑ Webb JC, Sun XM, McCarthy SN, Neuwirth C, Thompson GR, Knight BL, Soutar AK. Characterization of mutations in the low density lipoprotein (LDL)-receptor gene in patients with homozygous familial hypercholesterolemia, and frequency of these mutations in FH patients in the United Kingdom. J Lipid Res. 1996 Feb;37(2):368-81. PMID:9026534
↑ Peeters AV, Van Gaal LF, du Plessis L, Lombardi MP, Havekes LM, Kotze MJ. Mutational and genetic origin of LDL receptor gene mutations detected in both Belgian and Dutch familial hypercholesterolemics. Hum Genet. 1997 Aug;100(2):266-70. PMID:9254862
↑ Jensen HK, Jensen TG, Faergeman O, Jensen LG, Andresen BS, Corydon MJ, Andreasen PH, Hansen PS, Heath F, Bolund L, Gregersen N. Two mutations in the same low-density lipoprotein receptor allele act in synergy to reduce receptor function in heterozygous familial hypercholesterolemia. Hum Mutat. 1997;9(5):437-44. PMID:9143924 doi:<437::AID-HUMU10>3.0.CO;2-3 10.1002/(SICI)1098-1004(1997)9:5<437::AID-HUMU10>3.0.CO;2-3
↑ Day IN, Whittall RA, O'Dell SD, Haddad L, Bolla MK, Gudnason V, Humphries SE. Spectrum of LDL receptor gene mutations in heterozygous familial hypercholesterolemia. Hum Mutat. 1997;10(2):116-27. PMID:9259195 doi:<116::AID-HUMU4>3.0.CO;2-I 10.1002/(SICI)1098-1004(1997)10:2<116::AID-HUMU4>3.0.CO;2-I
↑ Leren TP, Tonstad S, Gundersen KE, Bakken KS, Rodningen OK, Sundvold H, Ose L, Berg K. Molecular genetics of familial hypercholesterolaemia in Norway. J Intern Med. 1997 Mar;241(3):185-94. PMID:9104431
↑ Gorski B, Kubalska J, Naruszewicz M, Lubinski J. LDL-R and Apo-B-100 gene mutations in Polish familial hypercholesterolemias. Hum Genet. 1998 May;102(5):562-5. PMID:9654205
↑ Couture P, Vohl MC, Gagne C, Gaudet D, Torres AL, Lupien PJ, Despres JP, Labrie F, Simard J, Moorjani S. Identification of three mutations in the low-density lipoprotein receptor gene causing familial hypercholesterolemia among French Canadians. Hum Mutat. 1998;Suppl 1:S226-31. PMID:9452094
↑ Thiart R, Loubser O, de Villiers JN, Marx MP, Zaire R, Raal FJ, Kotze MJ. Two novel and two known low-density lipoprotein receptor gene mutations in German patients with familial hypercholesterolemia. Hum Mutat. 1998;Suppl 1:S232-3. PMID:9452095
↑ Mak YT, Zhang J, Chan YS, Mak TW, Tomlinson B, Masarei JR, Pang CP. Possible common mutations in the low density lipoprotein receptor gene in Chinese. Hum Mutat. 1998;Suppl 1:S310-3. PMID:9452118
↑ Cenarro A, Jensen HK, Casao E, Civeira F, Gonzalez-Bonillo J, Rodriguez-Rey JC, Gregersen N, Pocovi M. Identification of recurrent and novel mutations in the LDL receptor gene in Spanish patients with familial hypercholesterolemia. Mutations in brief no. 135. Online. Hum Mutat. 1998;11(5):413. PMID:10206683 doi:<413::AID-HUMU16>3.0.CO;2-I 10.1002/(SICI)1098-1004(1998)11:5<413::AID-HUMU16>3.0.CO;2-I
↑ Motti C, Bertolini S, Rampa P, Trovatello G, Liberatoscioli L, Calandra S, Federici G, Cortese C. Two novel mutations consisting in minor gene rearrangements in the human low density lipoprotein receptor gene in Italian patients affected by familial hypercholesterolemia. Mutations in brief no. 194. Online. Hum Mutat. 1998;12(3):290. PMID:10660340
↑ Hirayama T, Yamaki E, Hata A, Tsuji M, Hashimoto K, Yamamoto M, Emi M. Five familial hypercholesterolemic kindreds in Japan with novel mutations of the LDL receptor gene. J Hum Genet. 1998;43(4):250-4. PMID:9852677 doi:10.1007/s100380050083
↑ Lee WK, Haddad L, Macleod MJ, Dorrance AM, Wilson DJ, Gaffney D, Dominiczak MH, Packard CJ, Day IN, Humphries SE, Dominiczak AF. Identification of a common low density lipoprotein receptor mutation (C163Y) in the west of Scotland. J Med Genet. 1998 Jul;35(7):573-8. PMID:9678702
↑ Ekstrom U, Abrahamson M, Floren CH, Tollig H, Wettrell G, Nilsson G, Sun XM, Soutar AK, Nilsson-Ehle P. An individual with a healthy phenotype in spite of a pathogenic LDL receptor mutation (C240F). Clin Genet. 1999 May;55(5):332-9. PMID:10422803
↑ Ebhardt M, Schmidt H, Doerk T, Tietge U, Haas R, Manns MP, Schmidtke J, Stuhrmann M. Mutation analysis in 46 German families with familial hypercholesterolemia: identification of 8 new mutations. Mutations in brief no. 226. Online. Hum Mutat. 1999;13(3):257. PMID:10090484 doi:<257::AID-HUMU15>3.0.CO;2-A 10.1002/(SICI)1098-1004(1999)13:3<257::AID-HUMU15>3.0.CO;2-A
↑ Hattori H, Nagano M, Iwata F, Homma Y, Egashira T, Okada T. Identification of recurrent and novel mutations in the LDL receptor gene in Japanese familial hypercholesterolemia. Mutation in brief no. 248. Online. Hum Mutat. 1999;14(1):87. PMID:10447263 doi:<87::AID-HUMU14>3.0.CO;2-N 10.1002/(SICI)1098-1004(1999)14:1<87::AID-HUMU14>3.0.CO;2-N
↑ Bertolini S, Cantafora A, Averna M, Cortese C, Motti C, Martini S, Pes G, Postiglione A, Stefanutti C, Blotta I, Pisciotta L, Rolleri M, Langheim S, Ghisellini M, Rabbone I, Calandra S. Clinical expression of familial hypercholesterolemia in clusters of mutations of the LDL receptor gene that cause a receptor-defective or receptor-negative phenotype. Arterioscler Thromb Vasc Biol. 2000 Sep;20(9):E41-52. PMID:10978268
↑ Miltiadous G, Elisaf M, Xenophontos S, Manoli P, Cariolou MA. Segregation of a novel LDLR gene mutation (I430T) with familial hypercholesterolaemia in a Greek pedigree. Hum Mutat. 2000 Sep;16(3):277. PMID:10980548 doi:<277::AID-HUMU24>3.0.CO;2-Y 10.1002/1098-1004(200009)16:3<277::AID-HUMU24>3.0.CO;2-Y
↑ Thiart R, Scholtz CL, Vergotine J, Hoogendijk CF, de Villiers JN, Nissen H, Brusgaard K, Gaffney D, Hoffs MS, Vermaak WJ, Kotze MJ. Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia. J Med Genet. 2000 Jul;37(7):514-9. PMID:10882754
↑ Takahashi M, Ikeda U, Takahashi S, Hattori H, Iwasaki T, Ishihara M, Egashira T, Honma S, Asano Y, Shimada K. A novel mutation in exon 2 of the low-density lipoprotein-receptor gene in a patient with homozygous familial hypercholesterolemia. Clin Genet. 2001 Apr;59(4):290-2. PMID:11298688
↑ Humphries SE, Whittall RA, Hubbart CS, Maplebeck S, Cooper JA, Soutar AK, Naoumova R, Thompson GR, Seed M, Durrington PN, Miller JP, Betteridge DJ, Neil HA. Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk. J Med Genet. 2006 Dec;43(12):943-9. PMID:17142622 doi:10.1136/jmg.2006.038356
↑ Abifadel M, Rabes JP, Jambart S, Halaby G, Gannage-Yared MH, Sarkis A, Beaino G, Varret M, Salem N, Corbani S, Aydenian H, Junien C, Munnich A, Boileau C. The molecular basis of familial hypercholesterolemia in Lebanon: spectrum of LDLR mutations and role of PCSK9 as a modifier gene. Hum Mutat. 2009 Jul;30(7):E682-91. doi: 10.1002/humu.21002. PMID:19319977 doi:10.1002/humu.21002
↑ Walus-Miarka M, Sanak M, Idzior-Walus B, Miarka P, Witek P, Malecki MT, Czarnecka D. A novel mutation (Cys308Phe) of the LDL receptor gene in families from the South-Eastern part of Poland. Mol Biol Rep. 2012 May;39(5):5181-6. doi: 10.1007/s11033-011-1314-0. Epub 2011, Dec 13. PMID:22160468 doi:10.1007/s11033-011-1314-0
↑ Kurniawan ND, Atkins AR, Bieri S, Brown CJ, Brereton IM, Kroon PA, Smith R. NMR structure of a concatemer of the first and second ligand-binding modules of the human low-density lipoprotein receptor. Protein Sci. 2000 Jul;9(7):1282-93. PMID:10933493

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1f5y"

@@ Line 1: / Line 1: @@
-[[Image:1f5y.gif|left|200px]]<br />
-<applet load="1f5y" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1f5y" />
-'''NMR STRUCTURE OF A CONCATEMER OF THE FIRST AND SECOND LIGAND-BINDING MODULES OF THE HUMAN LDL RECEPTOR'''<br />
-==Overview==
+==NMR STRUCTURE OF A CONCATEMER OF THE FIRST AND SECOND LIGAND-BINDING MODULES OF THE HUMAN LDL RECEPTOR==
-The ligand-binding domain of the human low-density lipoprotein receptor, consists of seven modules, each of 40-45 residues. In the presence of, calcium, these modules adopt a common polypeptide fold with three, conserved disulfide bonds. A concatemer of the first and second modules, (LB(1-2)) folds efficiently in the presence of calcium ions, forming the, same disulfide connectivities as in the isolated modules. The, three-dimensional structure of LB(1-2) has now been solved using, two-dimensional 1H NMR spectroscopy and restrained molecular dynamics, calculations. No intermodule nuclear Overhauser effects were observed, indicating the absence of persistent interaction between them. The near, random-coil NH and H alpha chemical shifts and the low phi and psi angle, order parameters of the four-residue linker suggest that it has, considerable flexibility. The family of LB(1-2) structures superimposed, well over LB1 or LB2, but not over both modules simultaneously. LB1 and, LB2 have a similar pattern of calcium ligands, but the orientations of the, indole rings of the tryptophan residues W23 and W66 differ, with the, latter limiting solvent access to the calcium ion. From these studies, it, appears that although most of the modules in the ligand-binding region of, the receptor are joined by short segments, these linkers may impart, considerable flexibility on this region.
+<StructureSection load='1f5y' size='340' side='right'caption='[[1f5y]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1f5y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F5Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F5Y FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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></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=1f5y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f5y OCA], [https://pdbe.org/1f5y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f5y RCSB], [https://www.ebi.ac.uk/pdbsum/1f5y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f5y 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/f5/1f5y_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1f5y ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The ligand-binding domain of the human low-density lipoprotein receptor consists of seven modules, each of 40-45 residues. In the presence of calcium, these modules adopt a common polypeptide fold with three conserved disulfide bonds. A concatemer of the first and second modules (LB(1-2)) folds efficiently in the presence of calcium ions, forming the same disulfide connectivities as in the isolated modules. The three-dimensional structure of LB(1-2) has now been solved using two-dimensional 1H NMR spectroscopy and restrained molecular dynamics calculations. No intermodule nuclear Overhauser effects were observed, indicating the absence of persistent interaction between them. The near random-coil NH and H alpha chemical shifts and the low phi and psi angle order parameters of the four-residue linker suggest that it has considerable flexibility. The family of LB(1-2) structures superimposed well over LB1 or LB2, but not over both modules simultaneously. LB1 and LB2 have a similar pattern of calcium ligands, but the orientations of the indole rings of the tryptophan residues W23 and W66 differ, with the latter limiting solvent access to the calcium ion. From these studies, it appears that although most of the modules in the ligand-binding region of the receptor are joined by short segments, these linkers may impart considerable flexibility on this region.
-==Disease==
+NMR structure of a concatemer of the first and second ligand-binding modules of the human low-density lipoprotein receptor.,Kurniawan ND, Atkins AR, Bieri S, Brown CJ, Brereton IM, Kroon PA, Smith R Protein Sci. 2000 Jul;9(7):1282-93. PMID:10933493<ref>PMID:10933493</ref>
-Known disease associated with this structure: Hypercholesterolemia, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606945 606945]]
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-F5Y 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 CA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1F5Y OCA].
+</div>
+<div class="pdbe-citations 1f5y" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-NMR structure of a concatemer of the first and second ligand-binding modules of the human low-density lipoprotein receptor., Kurniawan ND, Atkins AR, Bieri S, Brown CJ, Brereton IM, Kroon PA, Smith R, Protein Sci. 2000 Jul;9(7):1282-93. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10933493 10933493]
+*[[LDL receptor|LDL receptor]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Atkins, A.R.]]
+[[Category: Atkins AR]]
-[[Category: Brereton, I.M.]]
+[[Category: Brereton IM]]
-[[Category: Kroon, P.A.]]
+[[Category: Kroon PA]]
-[[Category: Kurniawan, N.D.]]
+[[Category: Kurniawan ND]]
-[[Category: Smith, R.]]
+[[Category: Smith R]]
-[[Category: CA]]
-[[Category: 3-10 helix]]
-[[Category: beta hairpin]]
-[[Category: calcium binding]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:49:37 2007''

1f5y

From Proteopedia

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NMR STRUCTURE OF A CONCATEMER OF THE FIRST AND SECOND LIGAND-BINDING MODULES OF THE HUMAN LDL RECEPTOR

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Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

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