Crystal structure of human apolipoprotein A-I: Insights into its protective effect against cardiovascular diseases

Ajees, A. Abdul; Anantharamaiah, G.M.; Mishra, Vinod; Hussain, M. Mahmood

doi:10.1073/pnas.0506877103

Cited by 201 publications

(220 citation statements)

References 52 publications

(60 reference statements)

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“…Finally, the authors used a publication recently retracted from the literature to support their model. They state, "…it is remarkable to note that the conformation of apoA-I in the (DSH) model contains several turns found in the recently reported crystal structure of lipid-free full-length apoA-I" (41).…”

Section: Discussionmentioning

confidence: 91%

Assessment of the Validity of the Double Superhelix Model for Reconstituted High Density Lipoproteins

Jones

Zhang

Catte

et al. 2010

Journal of Biological Chemistry

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High density lipoproteins (HDL) represent a heterogeneous population of particles with apoA-I as the major protein (1). Whether apoA-I/HDL 2 plays a direct role in cardiovascular disease prevention (e.g. removal of cholesterol from clogged arteries) or an indirect one (e.g. acts as a platform for the clustering of protective molecules, such as anti-inflammatory or antioxidant proteins), detailed knowledge of HDL structure is a key to understanding the molecular mechanism underlying these processes. Because the conformation of apoA-I on HDL is highly plastic (1), understanding apoA-I/HDL structure and dynamics is not straightforward.Since the early 1970s, the standard model for HDL particles reconstituted from apolipoprotein A-I (apoA-I) and phospholipid (apoA-I/HDL) has been that of a discoidal particle on the order of 100 Å in diameter and the thickness of a phospholipid bilayer. The initial observation of discoidal HDL particles was made by Forte et al. (2) when they examined HDL from patients with familial lecithin:cholesterol acyltransferase deficiency by negative stain EM. Reconstituted apoA-I/HDL particles (3) and nascent HDL from lymph (4) were then observed by negative stain EM to also have a discoidal shape. X-ray and neutron scattering studies (5, 6) provided further support for the standard discoidal model. The standard discoidal model has been used to interpret the results of a large number of experimental studies of the structure of reconstituted apoA-I/HDL particles. For review, see however, Wu et al. (11) used small angle neutron scattering to develop a model for apoA-I/HDL particles that is dramatically different from the standard model. In their model, termed a double superhelix (DSH), apoA-I possesses an open helical shape that twists around a central prolate ellipsoidal particle resembling a partial type I hexagonal lyotropic liquid crystalline phase.The DSH model is interesting. It is similar to MD simulation-based models (12) in that the proposed double superhelix forms a left-handed spiral as it wraps around the prolate ellip-

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Section: Discussionmentioning

confidence: 91%

Assessment of the Validity of the Double Superhelix Model for Reconstituted High Density Lipoproteins

Jones

Zhang

Catte

et al. 2010

Journal of Biological Chemistry

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“…ApoA-I is the major constituent of high-density lipoprotein (HDL) that plays an important role in reverse cholesterol transport, a process in which apoA-I acts as an acceptor for sequential transfer of phospholipids and free cholesterol from peripheral tissues and transport of cholesterol to the liver and other tissues for excretion and steroidogenesis. 19 All plasma lipoproteins can appear in the PDE similar to other macromolecules. 20 The peritoneal loss of HDL (may be up to 34% of its synthetic rate) is inversely correlated with the plasma HDL level.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Peritoneal Dialysate Fluid in Patients with Different Types of Peritoneal Membranes

et al. 2007

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Efficacy of peritoneal dialysis is determined by solute transport through peritoneal membranes. With the use of the peritoneal equilibration test (PET), peritoneal membranes can be classified as high (H), high average (HA), low average (LA), and low (L) transporters, based on the removal or transport rate of solutes, which are small molecules. Whether there is any difference in macromolecules (i.e., proteins) removed by different types of peritoneal membranes remains unclear. We performed a gel-based differential proteomics study of peritoneal dialysate effluents (PDE) obtained from chronic peritoneal dialysis (CPD) patients with H, HA, LA, and L transport rates (n = 5 for each group; total n = 20). Quantitative analysis and ANOVA with Tukey's posthoc multiple comparisons revealed five proteins whose abundance in PDE significantly differed among groups. These proteins were successfully identified by matrix-assisted laser desorption ionization quadrupole time-of-flight (MALDI-Q-TOF) mass spectrometry (MS) and tandem mass spectrometry (MS/MS) analyses, including serum albumin in a complex with myristic acid and triiodobenzoic acid, α1-antitrypsin, complement component C4A, immunoglobulin κ light chain, and apolipoprotein A-I. The differences among groups in PDE levels of C4A and immunoglobulin κ were clearly confirmed in a validation set of the other 24 patients (n = 6 for each group) using ELISA. These data may lead to better understanding of the physiology of peritoneal membrane transport in CPD patients. Extending the study to a larger number of patients with subgroup analyses may yield additional information of the peritoneal dialysate proteins in association with dialysis adequacy, residual renal function, nutritional status, and risk of peritoneal infection. Keywords: dialysate • kidney • membranes • peritoneal dialysis • proteome • renal failure • solute clearance

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“…To do this we used the maximum distance of C α -Lysine-(cross-linker)-C α -Lysine calculated for each of the crosslinkers; 22.3 Å, 26.6 Å, and 30.7 Å for DSG, DSP and EGS, respectively. Next, the apoA-I structure was constructed from coordinates from lipid-free Δ43-apoA-I (14) that were joined with the 1-43 amino acids reported for the crystal structure of full-length lipid-free apoA-I (27). Thirdly, apoA-I was bent only at the proline sites between the amphipathic segments of apoA-I.…”

Section: Molecular Modeling Of Lipid-free and Lipid-bound Apoa-imentioning

confidence: 99%

“…However, the X-ray crystal structure of full length lipid-free apoA-I has been recently reported by Ajees et al (27). These investigators were the first to show that full-length lipid-free apoA-I exists in a four-helix bundle.…”

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confidence: 99%

Conformational Adaptation of Apolipoprotein A-I to Discretely Sized Phospholipid Complexes

et al. 2007

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The conformational constraints for apoA-I bound to recombinant phospholipid complexes (rHDL) were attained from a combination of chemical cross-linking and mass spectrometry. Molecular distances were then used to refine models of lipid-bound apoA-I on both 80 and 96Å diameter rHDL particles. To obtain molecular constraints on the protein bound to phospholipid complexes, three different lysine-selective homo-bifunctional cross-linkers with increasing spacer arm lengths (i.e., 7.7, 12.0, and 16.1 Å) were reacted with purified, homogeneous recombinant 1-palmitoyl-2-oleoylsn-glycerol-3-phosphocholine (POPC) apoA-I rHDL complexes of each diameter. Cross-linked dimeric apoA-I products were separated from monomeric apoprotein using 12% SDS PAGE, then subjected to in-gel trypsin digest, and identified by MS/MS sequencing. These studies aid in the refinement of our previously published molecular model of 2 apoA-I molecules bound to ~150 molecules of POPC and suggest that the protein hydrophobic interactions at the N-and C-terminal domains decrease as the number of phospholipid molecules or "lipidation state" of apoA-I increases. Thus, it appears that these incremental changes in the interaction between the N-and C-terminal ends of apoA-I stabilize its tertiary conformation in the lipid-free state as well as allowing it to unfold and sequester discrete amounts of phospholipid molecules.Apolipoprotein A-I (apoA-I) is a 28 kDa protein synthesized by the liver and intestine and is responsible for modulating the formation, metabolism, and catabolism of high density lipoprotein cholesterol. HDL has been known for decades to be a negative risk factor for predicting the development of coronary artery disease in humans, but the specific mechanism (s) responsible for its protective role in cholesterol metabolism continues to be studied and elucidated (1-3).ApoA-I shares a number of similarities to other members of the apoprotein super gene family, as well as possessing a unique set of properties related to its unique role in lipid metabolism (4). Totally soluble in aqueous solution, apoA-I monomers exist in a lipid-free state, but also avidly bind to each other, as well as lipid surfaces (5). Although apoA-I readily binds lipid surfaces, the formation of small apoA-I containing phospholipid and cholesterol particles, an important step in HDL metabolism, does not occur to a significant extent in the absence of the ABCA1 transporter. During the formation of "nascent" HDL, monomers of lipid-free apoA-I bind to ABCA1 which adds phospholipid and cholesterol to yield a particle containing two 1To whom correspondence should be addressed: Dept. of Pathology, Section on Lipid Sciences, Wake Forest University Health Sciences, Medical Center Blvd., Winston-Salem, NC 27157. Tel.: 336-716-2147; Fax 336-716-6279; E-mail:msthomas@wfubmc.edu. NIH Public Access Author ManuscriptBiochemistry. Author manuscript; available in PMC 2008 September 25. Published in final edited form as:Biochemistry. -I (3,6,7). In this form, the conformation of ...

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Crystal structure of human apolipoprotein A-I: Insights into its protective effect against cardiovascular diseases

Cited by 201 publications

References 52 publications

Assessment of the Validity of the Double Superhelix Model for Reconstituted High Density Lipoproteins

Assessment of the Validity of the Double Superhelix Model for Reconstituted High Density Lipoproteins

Proteomic Analysis of Peritoneal Dialysate Fluid in Patients with Different Types of Peritoneal Membranes

Conformational Adaptation of Apolipoprotein A-I to Discretely Sized Phospholipid Complexes

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