The use of chemical cross-linking and mass spectrometry to elucidate the tertiary conformation of lipid-bound apolipoprotein A-I

Current Opinion in Lipidology

Volumn 17, Issue 3, 2006, Pages 214-220

  Thomas, Michael J ^a   Bhat, Shaila ^a   Sorci Thomas, Mary G ^a  

^a WAKE FOREST UNIVERSITY HEALTH SCIENCES   (United States)

Author keywords

Apolipoprotein A I; Chemical cross linking; Conformation; HDL; Mass spectrometry

Indexed keywords

APOLIPOPROTEIN A1; LIPID;

AMINO ACID SEQUENCE; AMINO TERMINAL SEQUENCE; CARBOXY TERMINAL SEQUENCE; CROSS LINKING; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; MASS SPECTROMETRY; MUTATION; NUCLEAR MAGNETIC RESONANCE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN LIPID INTERACTION; PROTEIN STABILITY; PROTEIN STRUCTURE; REVIEW; X RAY;

APOLIPOPROTEIN A-I; CROSS-LINKING REAGENTS; LIPIDS; MASS SPECTROMETRY; MODELS, MOLECULAR; PROTEIN STRUCTURE, TERTIARY;

EID: 33646858367     PISSN: 09579672     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.mol.0000226111.05060.f4     Document Type: Review

References (57)

1. Oram JF, Heinecke JW. ATP-binding cassette transporter A1: a cell cholesterol exporter that protects against cardiovascular disease. Physiol Rev 2005; 85:1343-1372.
2. Timmins JM, Lee JY, Boudyguina E, et al. Targeted inactivation of hepatic Abcal causes profound hypoalphalipoproteinemia and kidney hypercatabolism of apoA-I. J Clin Invest 2005; 115:1333-1342.
3. Curtiss LK, Valenta DT, Hime NJ, et al. What is so special about apolipoprotein AI in reverse cholesterol transport? Arterioscler Thromb Vasc Biol 2006; 26:12-19. Excellent review of current studies concerning apoA-I lipidation and remodeling. Since macrophages do not synthesize apoA-I, but do synthesize PLTP, CETP and lipoprotein lipase it has been hypothesized that remodeling of spherical HDL occurs within the intima generating substrate for transport of excess macrophage cholesterol to lipid-poor apoA-I.
4. von Eckardstein A. Differential diagnosis of familial high density lipoprotein deficiency syndromes. Atherosclerosis 2005; 9 December [Epub ahead of print]. Review of monogenic HDL deficiencies and their relationship to defects in apoA-I, LCAT, or ABCA1 genes. Discusses differential diagnostic procedures for individuals with HDL cholesterol levels below the fifth percentile.
5. Sorci-Thomas MG, Thomas MJ. The effects of altered apolipoprotein A-I structure on plasima HDL concentration. Trends Cardiovasc Med 2002; 12:121-128.
6. Thuahnai ST, Lund-Katz S, Dhanasekaran P, et al. Scavenger receptor class B type I-mediated cholesteryl ester-selective uptake and efflux of unesterified cholesterol: influence of high density lipoprotein size and structure. J Biol Chem 2004; 279:12448-12455.
7. Connelly MA, Williams DL. SR-BI and HDL cholesteryl ester metabolism. Endocr Res 2004; 30:697-703.
8. Chan L. The apolipoprotein multigene family: structure, expression, evolution, and molecular genetics. Klin Wochenschr 1989; 67:225-237.
9. Brouillette CG, Anantharamaiah GM, Engler JA, et al. Structural models of human apolipoprotein A-I: a critical analysis and review. Biochim Biophys Acta 2001; 1531:4-46.
10. Borhani DW, Rogers DP, Engler JA, et al. Crystal structure of truncated human apolipoprotein A-I suggests a lipid-bound conformation. Proc Natl Acad Sci U S A 1997; 94:12291-12296.
11. Segrest JP, Garber DW, Brouillette CG, et al. The amphipathic α-helix: a multifunctional structural motif in plasma apolipoproteins. Adv Protein Chem 1994; 45:303-369.
12. Segrest JP, Jackson RL, Morrisett JD, et al. A molecular theory of lipid-protein interactions in the plasma lipoproteins. FEBS Lett 1974; 38:247-253.
13. Alexander ET, Bhat S, Thomas MJ, et al. Apolipoprotein A-I helix 6 negatively charged residues attenuate lecithin : cholesterol acyltransferase (LCAT) reactivity. Biochemistry 2005; 44:5409-5419. Investigations into the role negatively charged apoA-I helix 6 residues play in the activation of LCAT. Concludes that intra-helical salt bridging between highly conserved negatively and positively charged residues in helix 6 are the basis for forming a conformation-optimizing interaction between activator and enzyme.
14. Roosbeek S, Vanloo B, Duverger N, et al. Three arginine residues in apolipoprotein A-I are critical for activation of lecithin: cholesterol acyltransferase. J Lipid Res 2001; 42:31-40.
15. Gorshkova IN, Liu T, Kan HY, et al. Structure and stability of apolipoprotein a-I in solution and in discoidal high-density lipoprotein probed by double charge ablation and deletion mutation. Biochemistry 2006; 45:1242-1254. Study of four double charge ablation mutations within apoA-I helices 4, 5 and 6. Provides the first experimental evidence for stabilization of HDL by specific electrostatic inter-helical interactions, supporting the double belt model.
16. Fang YL, Gursky O, Atkinson D. Lipid-binding studies of human apolipoprotein A-I and its terminally truncated mutants. Biochemistry 2003; 42:13260-13268.
17. Fang Y, Gursky O, Atkinson D. Structural studies of N- and C-terminally truncated human apolipoprotein A-I. Biochemistry 2003; 42:6881-6890.
18. Saito H, Dhanasekaran P, Nguyen D, et al. Domain structure and lipid interaction in human apolipoproteins A-I and E, a general model. J Biol Chem 2003; 278:23227-23232.
19. Marcel YL, Kiss RS. Structure-function relationships of apolipoprotein A-I: a flexible protein with dynamic lipid associations. Curr Opin Lipidol 2003; 14:151-157.
20. McManus DC, Scott BR, Frank PG, et al. Distinct central amphipathic α-helices in apolipoprotein A-I contribute to the in vivo maturation of high density lipoprotein by either activating lecithin-cholesterol acyltransferase or binding lipids. J Biol Chem 2000; 275:5043-5051.
21. Bhat S, Zabalawi M, Willingham MC, et al. Quality control in the apoA-I secretory pathway: alterations in apoA-I conformation lead to its retention in the cytoplasm. J Lipid Res 2004; 45:1207-1220.
22. Minnich A, Collet X, Roghani A, et al. Site-directed mutagenesis and structure-function analysis of the human apolipoprotein A-I: relation between lecithin-cholesterol acyltransferase activation and lipid binding. J Biol Chem 1992; 267:16553-16560.
23. Sorci-Thomas M, Kearns MW, Lee JP. Apolipoprotein A-I domains involved in lecithin-cholesterol acyltransferase activation: structure : function relationships. J Biol Chem 1993; 268:21403-21409.
24. Chroni A, Duka A, Kan HY, et al. Point mutations in apolipoprotein A-I mimic the phenotype observed in patients with classical lecithin: cholesterol acyltransferase deficiency. Biochemistry 2005; 44:14353-14366. In-vivo studies of apoA-I point mutations and their physiological impact on HDL metabolism. Concludes that certain mutations block conversion of discoidal particles to spherical particles and lead to phenotypes similar to HDL and LCAT deficiencies.
25. McManus DC, Scott BR, Franklin V, et al. Proteolytic degradation and impaired secretion of an apolipoprotein A-I mutant associated with dominantly inherited hypoalphalipoproteinemia. J Biol Chem 2001; 276:21292-21302.
26. Sorci-Thomas MG, Thomas M, Curtiss L, et al. Single repeat deletion in apoA-I blocks cholesterol esterification and results in rapid catabolism of Δ6 and wild-type apoA-I in transgenic mice. J Biol Chem 2000; 275:12156-12163.
27. Bielicki JK, McCall MR, Stoltzfus LJ, et al. Evidence that apolipoprotein A-I Milano has reduced capacity, compared with wild-type apolipoprotein A-I, to recruit membrane cholesterol. Arterioscler Thromb Vasc Biol 1997; 17:1637-1643.
28. Ajees AA, Anantharamaiah GM, Mishra VK, et al. Crystal structure of human apolipoprotein A-I: insights into its protective effect against cardiovascular diseases. Proc Natl Acad Sci U S A 2006; 103:2126-2131. The 2.4 Å crystal structure of native, lipid-free apoA-I is presented in this article. Full-length apoA-I crystallized as an N-terminal four-helix bundle and two C-terminal helices. This should be compared with the horseshoe or saddle structure of truncated apoA-I reported earlier [10]. This study conclusively shows that the N-terminal domain is essential in maintaining the lipid-free conformation of apoA-I.
29. Klon AE, Segrest JP, Harvey SC. Comparative models for human apolipoprotein A-I bound to lipid in discoidal high-density lipoprotein particles. Biochemistry 2002; 41:10895-10905.
30. Koppaka V, Silvestro L, Engler JA, et al. The structure of human lipoprotein A-I: evidence for the 'belt model'. J Biol Chem 1999; 274:14541-14544.
31. Maiorano JN, Davidson WS. The orientation of helix 4 in apolipoprotein A-I-containing reconstituted high density lipoproteins. J Biol Chem 2000; 275:17374-17380.
32. Li HH, Lyles DS, Thomas MJ, et al. Structural determination of lipid-bound ApoA-I using fluorescence resonance energy transfer. J Biol Chem 2000; 275:37048-37054.
33. Segrest JP, Jones MK, Klon AE, et al. A detailed molecular belt model for apolipoprotein A-I in discoidal high density lipoprotein. J Biol Chem 1999; 274:31755-31758.
34. Panagotopulos SE, Horace EM, Maiorano JN, et al. Apolipoprotein A-I adopts a belt-like orientation in reconstituted high density lipoproteins. J Biol Chem 2001; 276:42965-42970.
35. Klon AE, Segrest JP, Harvey SC. Molecular dynamics simulations on discoidal HDL particles suggest a mechanism for rotation in the apo A-I belt model. J Mol Biol 2002; 324:703-721.
36. Li H-h, Lyles DS, Pan W, et al. Apo A-I structure on discs and spheres: variable helix registry and conformational states. J Biol Chem 2002; 42:39093-39101.
37. Tricerri MA, Behling Agree AK, Sanchez SA, et al. Arrangement of apolipoprotein A-I in reconstituted high-density lipoprotein disks: an alternative model based on fluorescence resonance energy transfer experiments. Biochemistry 2001; 40:5065-5074.
38. Corsico B, Toledo JD, Garda HA. Evidence for a central apolipoprotein A-I domain loosely bound to lipids in discoidal lipoproteins that is capable of penetrating the bilayer of phospholipid vesicles. J Biol Chem 2001; 276:16978-16985.
39. Maiorano JN, Jandacek RJ, Horace EM, et al. Identification and structural ramifications of a hinge domain in apolipoprotein A-I discoidal high-density lipoproteins of different size. Biochemistry 2004; 43:11717-11726.
40. Li L, Chen J, Mishra VK, et al. Double belt structure of discoidal high density lipoproteins: molecular basis for size heterogeneity. J Mol Biol 2004; 343:1293-1311.
41. Young MM, Tang N, Hempel JC, et al. High throughput protein fold identification by using experimental constraints derived from intramolecular cross-links and mass spectrometry. Proc Natl Acad Sci U S A 2000; 97:5802-5806.
42. Huang BX, Dass C, Kim HY. Probing conformational changes of human serum albumin due to unsaturated fatty acid binding by chemical cross-linking and mass spectrometry. Biochem J 2005; 387:695-702. Chemical cross-linking and mass spectrometry was used to probe the conformational changes of human serum albumin (HSA) upon the binding of fatty acids. The results suggest that in solution HSA adopts distinctively different conformations when mono as compared with polyunsaturated fatty acids are bound. Overall, these observations agree well with X-ray crystallographic studies. It was noted, however, that most cross-linked lysine pairs were shorter than the crystal structure predicted.
43. Huang BX, Kim HY, Dass C. Probing three-dimensional structure of bovine serum albumin by chemical cross-linking and mass spectrometry. J Am Soc Mass Spectrom 2004; 15:1237-1247.
44. Swaim CL, Smith DL, Smith JB. The reaction of alpha-crystallin with the cross-linker 3,3′-dithiobis(sulfosuccinimidyl propionate) demonstrates close proximity of the C termini of alphaA and alphaB in the native assembly unexpected products from the reaction of the synthetic cross-linker 3,3′-dithiobis(sulfosuccinimidyl propionate), DTSSP with peptides. Protein Sci 2004; 13:2832-2835.
45. Onisko B, Fernandez EG, Freire ML, et al. Probing PrPSc structure using chemical cross-linking and mass spectrometry: evidence of the proximity of Gly90 amino termini in the Pr27-30 aggregate. Biochemistry 2005; 44:10100-10109.
46. Olayioye MA, Vehring S, Muller P, et al. StarD10, a START domain protein overexpressed in breast cancer, functions as a phospholipid transfer protein. J Biol Chem 2005; 280:27436-27442.
47. Kalkhof S, Ihling C, Mechtler K, et al. Chemical cross-linking and high-performance Fourier transform ion cyclotron resonance mass spectrometry for protein interaction analysis: application to a calmodulin/target peptide complex. Anal Chem 2005; 77:495-503.
48. Schmidt A, Kalkhof S, Ihling C, et al. Mapping protein interfaces by chemical cross-linking and Fourier transform ion cyclotron resonance mass spectrometry: application to a calmodulin/adenylyl cyclase 8 peptide complex. Eur J Mass Spectrom (Chichester, Eng) 2005; 11:525-534.
49. Sinz A, Kalkhof S, Ihling C. Mapping protein interfaces by a trifunctional cross-linker combined with MALDI-TOF and ESI-FTICR mass spectrometry. J Am Soc Mass Spectrom 2005; 16:1921-1931.
50. Swaim CL, Smith JB, Smith DL. Unexpected products from the reaction of the synthetic cross-linker 3,3′-dithiobis(sulfosuccinimidyl propionate), DTSSP with peptides. J Am Soc Mass Spectrom 2004; 15:736-749.
51. Green NS, Reisler E, Houk KN. Quantitative evaluation of the lengths of homobifunctional protein cross-linking reagents used as molecular rulers. Protein Sci 2001; 10:1293-1304.
52. Bhat S, Sorci-Thomas MG, Alexander ET, et al. Intermolecular contact between globular N-terminal fold and C-terminal domain of ApoA-I stabilizes its lipid-bound conformation: studies employing chemical cross-linking and mass spectrometry. J Biol Chem 2005; 280:33015-33025. Cross-linking/MS/MS of 96 Å recombinant HDL were treated with the amine-specific cross-linker DSP at varying molar ratios. At 2:1 molar ratio of cross-links to apoA-I, two distinct cross-linked products were isolated and sequenced and found to correspond to cross-links in different regions of the protein. Tandem mass spectrometry with MS/MS sequencing of cross-linked peptides showed a distinct conformation for lipid-bound apoA-I in which the N termini domain folds back onto itself as well as interacting with the C-terminal domain.
53. Davidson WS, Hilliard GM. The spatial organization of apolipoprotein A-I on the edge of discoidal high density lipoprotein particles: a mass spectrometry study. J Biol Chem 2003; 278:27199-27207.
54. Silva RA, Hilliard GM, Li L, et al. A mass spectrometric determination of the conformation of dimeric apolipoprotein A-I in discoidal high density lipoproteins. Biochemistry 2005; 44:8600-8607. CCL/MS suggests two different conformations of the 'double-belt' arrangement in which two apoA-I molecules wrap around the 96 Å lipid disc in an antiparallel orientation with helix 5 of each apoA-I molecule across from each other. A second antiparallel orientation was detected indicating that helix 5 and helix 2 of two apoA-I molecules were adjacent to each other. The 78 Å lipid disc with two molecules of apoA-I fit a similar double-belt conformation. Mass spectrometric detection with MS/MS sequencing was used to identify cross-linked peptides.
55. Davidson WS, Silva RA. Apolipoprotein structural organization in high density lipoproteins: belts, bundles, hinges and hairpins. Curr Opin Lipidol 2005; 16:295-300. Summarizes recent advances towards an understanding of the three-dimensional structure of apoA-I on HDL with specific focus on high-resolution models.
56. Beckstead JA, Block BL, Bielicki JK, et al. Combined N- and C-terminal truncation of human apolipoprotein A-I yields a folded, functional central domain. Biochemistry 2005; 44:4591-4599.
57. Zhu HL, Atkinson D. Conformation and lipid binding of the N-terminal (1-44) domain of human apolipoprotein A-I. Biochemistry 2004; 43:13156-13164.