title: Molecular structure of low density lipoprotein: current status and future challenges.
abstract: This review highlights recent advances in structural studies on low density lipoprotein (LDL) with particular emphasis on the apolipoprotein moiety of LDL, apolipoprotein B100 (apoB100). Various molecular aspects of LDL are outlined and obstacles to structure determination are addressed. In this context, the prevailing conceptions of the molecular assembly of LDL and how the synergy of complementary biochemical, biophysical and molecular simulation approaches has lead to the current structural model of LDL are discussed. Evidence is presented that structural heterogeneity and the intrinsic dynamics of LDL are key determinants of the functionality of LDL in both health and disease. Some key research directions, remaining open questions and rapidly emerging new concepts for medical applications of LDL, are furthermore outlined. The article concludes by providing an outlook concerning promising future strategies for the clarification of the molecular details of LDL, in particular of apoB100, combining recent advances in molecular modeling with developments of novel experimental techniques. Although new insights into the molecular organization of LDL are forthcoming, many open questions remain unanswered. The major challenge of the next decade will certainly be the elucidation of the molecular structural and dynamic features of apoB100.
authors.affiliation: Institute of Biophysics and Nanosystems Research, Austrian Academy of Sciences, Schmiedlstr. 6, 8042 Graz, Austria. ruth.prassl@oeaw.ac.at
authors.forename: Ruth
authors.initials: R
authors.lastname: Prassl
authors.forename: Peter
authors.initials: P
authors.lastname: Laggner
mesh_terms: D053299:Apolipoprotein B-100 / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure*; D015394:Molecular Structure; D012106:Research / Q000639:trends; D013329:Structure-Activity Relationship
chemical_list: D053299:Apolipoprotein B-100; D008077:Lipoproteins, LDL
references.citation: J Lipid Res. 1997 Feb;38(2):324-42
references.pmid: 9162752
references.citation: J Lipid Res. 1991 Nov;32(11):1741-53
references.pmid: 1770294
references.citation: Proc Natl Acad Sci U S A. 2006 May 2;103(18):6871-6
references.pmid: 16636271
references.citation: Eur J Biochem. 1978 Mar;84(1):227-32
references.pmid: 206433
references.citation: J Lipid Res. 2001 Sep;42(9):1346-67
references.pmid: 11518754
references.citation: Science. 1976 Jan 16;191(4223):150-4
references.pmid: 174194
references.citation: J Biol Chem. 1989 Aug 25;264(24):14369-75
references.pmid: 2668286
references.citation: Biochemistry. 1986 Apr 8;25(7):1562-8
references.pmid: 3707893
references.citation: Arterioscler Thromb Vasc Biol. 2005 Aug;25(8):1536-40
references.pmid: 16055756
references.citation: Biochemistry. 1995 Mar 21;34(11):3795-801
references.pmid: 7893676
references.citation: J Biol Chem. 1996 Nov 15;271(46):28731-3
references.pmid: 8910510
references.citation: Adv Protein Chem. 1994;45:205-48
references.pmid: 8154370
references.citation: J Biol Chem. 1998 Mar 27;273(13):7244-51
references.pmid: 9516417
references.citation: Biochemistry. 2003 Dec 23;42(50):14988-93
references.pmid: 14674775
references.citation: Biochemistry. 1998 Sep 15;37(37):12867-74
references.pmid: 9737865
references.citation: Nature. 1986 Oct 23-29;323(6090):734-8
references.pmid: 3773997
references.citation: J Mol Biol. 1993 Dec 5;234(3):779-815
references.pmid: 8254673
references.citation: J Biol Chem. 1985 Apr 25;260(8):5067-72
references.pmid: 2580831
references.citation: Eur Biophys J. 2007 Nov;36(8):995-1013
references.pmid: 17611751
references.citation: J Biol Chem. 1988 Sep 25;263(27):13831-8
references.pmid: 3138240
references.citation: J Biol Chem. 2006 Jul 14;281(28):19732-9
references.pmid: 16704977
references.citation: Chem Phys Lipids. 1984 Dec;36(2):111-9
references.pmid: 6532566
references.citation: J Lipid Res. 1995 Sep;36(9):2027-37
references.pmid: 8558090
references.citation: J Biol Chem. 1991 Mar 25;266(9):5955-62
references.pmid: 2005131
references.citation: J Lipid Res. 1988 Jul;29(7):937-47
references.pmid: 2457642
references.citation: Proc Natl Acad Sci U S A. 1977 Mar;74(3):1042-6
references.pmid: 191827
references.citation: Eur Heart J. 1998 Feb;19 Suppl A:A24-30
references.pmid: 9519339
references.citation: Int J Pharm. 2007 Jan 2;328(1):86-94
references.pmid: 16959446
references.citation: Neoplasia. 2006 Jun;8(6):488-98
references.pmid: 16820095
references.citation: Structure. 1998 Jul 15;6(7):895-909
references.pmid: 9687371
references.citation: J Lipid Res. 1996 Sep;37(9):1915-23
references.pmid: 8895057
references.citation: Biochim Biophys Acta. 1990 Aug 28;1046(1):64-72
references.pmid: 2397246
references.citation: J Lipid Res. 1990 Jun;31(6):1051-62
references.pmid: 2373955
references.citation: Metabolism. 1992 Mar;41(3):229-35
references.pmid: 1542259
references.citation: Nature. 1986 Oct 23-29;323(6090):738-42
references.pmid: 3095664
references.citation: Proteins. 2007 Feb 1;66(2):342-58
references.pmid: 17109403
references.citation: Biochemistry. 1984 Oct 23;23(22):5343-52
references.pmid: 6095895
references.citation: Biochemistry. 1983 Jun 21;22(13):3170-8
references.pmid: 6882744
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17707-12
references.pmid: 17098868
references.citation: J Cell Biol. 1980 Dec;87(3 Pt 1):555-61
references.pmid: 7462316
references.citation: Curr Opin Lipidol. 2000 Oct;11(5):465-71
references.pmid: 11048889
references.citation: J Biol Chem. 1994 Apr 1;269(13):9409-12
references.pmid: 8144523
references.citation: J Biol Chem. 2000 May 26;275(21):16267-74
references.pmid: 10747912
references.citation: J Lipid Res. 1989 Mar;30(3):415-22
references.pmid: 2498452
references.citation: Atherosclerosis. 2003 Dec;171(2):245-53
references.pmid: 14644393
references.citation: J Lipid Res. 1998 Jun;39(6):1263-73
references.pmid: 9643358
references.citation: Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8420-5
references.pmid: 10411890
references.citation: J Lipid Res. 2003 Jan;44(1):22-32
references.pmid: 12518019
references.citation: J Biol Chem. 1988 Nov 15;263(32):16842-8
references.pmid: 3182816
references.citation: Hoppe Seylers Z Physiol Chem. 1977 Jul;358(7):771-8
references.pmid: 196994
references.citation: Chem Phys Lipids. 2003 Apr;123(2):193-207
references.pmid: 12691852
references.citation: Proc Natl Acad Sci U S A. 1984 Jul;81(14):4389-93
references.pmid: 6589601
references.citation: Biochim Biophys Acta. 1998 Jan 15;1389(2):112-22
references.pmid: 9461252
references.citation: Acta Crystallogr D Biol Crystallogr. 2001 Jan;57(Pt 1):108-21
references.pmid: 11134933
references.citation: Atherosclerosis. 1998 Aug;139(2):205-22
references.pmid: 9712326
references.citation: J Mol Biol. 1999 Jan 8;285(1):391-408
references.pmid: 9878414
references.citation: Curr Opin Lipidol. 1996 Jun;7(3):167-71
references.pmid: 8818515
references.citation: Nature. 2002 Jun 13;417(6890):750-4
references.pmid: 12066187
references.citation: Biochem Biophys Res Commun. 1978 Jun 29;82(4):1332-9
references.pmid: 212043
references.citation: Biochemistry. 1977 Jul 26;16(15):3487-91
references.pmid: 196635
references.citation: Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2509-13
references.pmid: 7708675
references.citation: Nat Med. 2002 Nov;8(11):1218-26
references.pmid: 12411948
references.citation: Isr J Med Sci. 1991 Feb;27(2):70-4
references.pmid: 2004886
references.citation: Biochemistry. 1976 Apr 6;15(7):1516-22
references.pmid: 177043
references.citation: Curr Opin Lipidol. 1997 Oct;8(5):246-52
references.pmid: 9335947
references.citation: Q Rev Biophys. 2007 Aug;40(3):191-285
references.pmid: 18078545
references.citation: J Lipid Res. 1997 Apr;38(4):659-69
references.pmid: 9144081
references.citation: Biochem Biophys Res Commun. 1986 Sep 30;139(3):1078-85
references.pmid: 3767991
references.citation: J Mol Biol. 1979 Jul 5;131(3):435-73
references.pmid: 229228
references.citation: J Biol Chem. 1995 Apr 21;270(16):9192-6
references.pmid: 7721835
references.citation: Curr Opin Lipidol. 1996 Oct;7(5):265-8
references.pmid: 8937514
references.citation: Int J Cardiol. 2000 Jun 30;74 Suppl 1:S17-22
references.pmid: 10856769
references.citation: Biochemistry. 1995 Jul 25;34(29):9571-80
references.pmid: 7626627
references.citation: J Lipid Res. 1993 Feb;34(2):295-308
references.pmid: 8429263
references.citation: FEBS Lett. 2003 Jan 2;533(1-3):21-4
references.pmid: 12505152
references.citation: J Biol Chem. 1992 Dec 5;267(34):24217-22
references.pmid: 1447171
references.citation: Arterioscler Thromb Vasc Biol. 2002 Feb 1;22(2):211-7
references.pmid: 11834518
references.citation: Circulation. 1990 Aug;82(2):495-506
references.pmid: 2372896
references.citation: Q Rev Biophys. 1978 Aug;11(3):371-425
references.pmid: 223189
references.citation: Biochemistry. 2005 Feb 1;44(4):1163-73
references.pmid: 15667210
references.citation: J Lipid Res. 1990 Jun;31(6):1109-20
references.pmid: 2373961
references.citation: Curr Opin Lipidol. 2006 Oct;17(5):502-9
references.pmid: 16960498
references.citation: J Biol Chem. 1986 Oct 5;261(28):12918-21
references.pmid: 3759943
references.citation: Nature. 2000 Sep 14;407(6801):233-41
references.pmid: 11001066
references.citation: Science. 1975 Oct 24;190(4212):392-4
references.pmid: 170681
references.citation: Biochim Biophys Acta. 1990 Jan 19;1037(1):48-57
references.pmid: 2294970
references.citation: J Biol Chem. 1994 Nov 18;269(46):29121-8
references.pmid: 7961878
references.citation: Biochim Biophys Acta. 1989 Aug 21;984(1):81-7
references.pmid: 2765542
references.citation: J Lipid Res. 2000 Apr;41(4):546-53
references.pmid: 10744775
references.citation: Annu Rev Biophys Biophys Chem. 1986;15:403-56
references.pmid: 3521660
references.citation: J Lipid Res. 1988 Apr;29(4):442-58
references.pmid: 3392462
references.citation: J Biol Chem. 1977 Jan 25;252(2):744-54
references.pmid: 188825
references.citation: J Lipid Res. 1996 Sep;37(9):1924-35
references.pmid: 8895058
references.citation: Biochim Biophys Acta. 2000 Nov 15;1488(3):189-210
references.pmid: 11082530
references.citation: Biochim Biophys Acta. 1975 Feb 20;380(2):320-7
references.pmid: 164237
references.citation: Curr Opin Lipidol. 2006 Aug;17(4):412-7
references.pmid: 16832165
references.citation: J Clin Invest. 1998 Mar 1;101(5):1084-93
references.pmid: 9486979
references.citation: Biophys J. 2007 Jun 1;92(11):4097-108
references.pmid: 17369413
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17757-62
references.pmid: 16306263
references.citation: Proteins. 1997 Jun;28(2):293-7
references.pmid: 9188746
references.citation: J Biol Chem. 1999 Jan 15;274(3):1334-41
references.pmid: 9880504
references.citation: J Lipid Res. 1999 Aug;40(8):1401-16
references.pmid: 10428976
references.citation: J Clin Invest. 1993 May;91(5):1926-33
references.pmid: 8387537
references.citation: J Lipid Res. 1986 Mar;27(3):316-25
references.pmid: 3734628
references.citation: Bioconjug Chem. 1994 Mar-Apr;5(2):105-13
references.pmid: 8031872
references.citation: J Protein Chem. 1989 Dec;8(6):689-99
references.pmid: 2624682
references.citation: Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15047-50
references.pmid: 8986761
references.citation: N Engl J Med. 1989 Apr 6;320(14):915-24
references.pmid: 2648148
references.citation: J Biol Chem. 1984 Jul 10;259(13):8522-8
references.pmid: 6564130
references.citation: Biochemistry. 2002 Jun 4;41(22):6978-87
references.pmid: 12033930
references.citation: Eur J Biochem. 1996 Mar 1;236(2):436-42
references.pmid: 8612613
references.citation: J Biol Chem. 1981 Nov 25;256(22):11832-9
references.pmid: 7298632
references.citation: Arch Biochem Biophys. 2004 Dec 1;432(1):122-7
references.pmid: 15519303
references.citation: Contrast Media Mol Imaging. 2007 Jan-Feb;2(1):16-23
references.pmid: 17318917
references.citation: J Biochem. 1980 Nov;88(5):1349-57
references.pmid: 7462184
references.citation: J Biol Chem. 2003 Nov 7;278(45):44702-7
references.pmid: 12941937
references.citation: Biophys J. 1995 May;68(5):2115-23
references.pmid: 7612855
references.citation: J Mol Biol. 1979 Jul 5;131(3):475-84
references.pmid: 229229
references.citation: J Biol Chem. 1997 Apr 11;272(15):10279-86
references.pmid: 9092579
references.citation: Acta Med Scand Suppl. 1987;715:51-9
references.pmid: 3035881
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19243-8
references.pmid: 17159147
references.citation: J Biol Chem. 1998 Dec 25;273(52):35355-61
references.pmid: 9857078
references.citation: Arterioscler Thromb. 1994 Oct;14(10):1674-85
references.pmid: 7918318
references.citation: J Lipid Res. 2000 Sep;41(9):1464-72
references.pmid: 10974054
references.citation: Arterioscler Thromb Vasc Biol. 1995 Apr;15(4):452-9
references.pmid: 7749856
references.citation: Adv Drug Deliv Rev. 2001 Apr 25;47(2-3):251-76
references.pmid: 11311995
references.citation: J Control Release. 2007 Dec 20;124(3):163-71
references.pmid: 17964677