Lysophospholipids play important roles in cellular signal transduction and are implicated in many biological processes, including tumorigenesis, angiogenesis, immunity, atherosclerosis, arteriosclerosis, cancer and neuronal survival. The intracellular transport of lysophospholipids is through FA (fatty acid)-binding protein. Lysophospholipids are also found in the extracellular space. However, the transport mechanism of lysophospholipids in the extracellular space is unknown. HSA (human serum albumin) is the most abundant carrier protein in blood plasma and plays an important role in determining the absorption, distribution, metabolism and excretion of drugs. In the present study, LPE (lysophosphatidylethanolamine) was used as the ligand to analyse the interaction of lysophospholipids with HSA by fluorescence quenching and crystallography. Fluorescence measurement showed that LPE binds to HSA with a Kd (dissociation constant) of 5.6 μM. The presence of FA (myristate) decreases this binding affinity (Kd of 12.9 μM). Moreover, we determined the crystal structure of HSA in complex with both myristate and LPE and showed that LPE binds at Sudlow site I located in subdomain IIA. LPE occupies two of the three subsites in Sudlow site I, with the LPE acyl chain occupying the hydrophobic bottom of Sudlow site I and the polar head group located at Sudlow site I entrance region pointing to the solvent. This orientation of LPE in HSA suggests that HSA is capable of accommodating other lysophospholipids and phospholipids. The study provides structural information on HSA–lysophospholipid interaction and may facilitate our understanding of the transport and distribution of lysophospholipids.
- binding site
- fluorescence quenching
- human serum albumin (HSA)
- lysophosphatidylethanolamine (LPE)
- X-ray-crystallographic structure
Phospholipids are important components of cell membrane. The hydrolysis of phospholipids by phospholipases leads to FAs (fatty acids) and lysoPLs (lysophospholipids), including LPA (lysophosphatidic acid), LPC (lysophosphatidylcholine), LPE (lysophosphatidylethanolamine), LPS (lysophosphatidylserine) and LPG (lysophosphatidylglycerol) (Figure 1). The functional roles of phospholipids and lysoPLs in cellular signal transduction are now well recognized (see [1,2] for reviews). LysoPLs are implicated in many biological processes, including tumorigenesis, angiogenesis, immunity, atherosclerosis, cancer and neuronal survival . High levels of lysoPLs cause potent cytotoxicity and are associated with some disease states (e.g. myocardial ischaemia and atherosclerosis) . LPC can increase vascular endothelium permeability and up-regulate the expression level of adhesion molecules and cytokines in monocytes , leading to the functional alterations in vasculature that are potentially involved in atherosclerosis . A growing family of G-protein-coupled receptors has been identified as high-affinity lysoPL receptors with evolutionarily conserved sequences that can activate the downstream signalling cascades and eventually lead to lysoPL-induced cellular functions . For example, LPA binds to specific receptors coupled to G-proteins [8–11] and induces various biological responses, such as cell proliferation, platelet aggregation and intracellular stress-fibre formation [8,9]. LPE was detected in human serum and was found to induce neuronal differentiation of PC12 cells  (a cell line derived from a phaeochromocytoma of the rat adrenal medulla) and stimulate chemotactic migration and cellular invasion in SK-OV3 human ovarian-cancer cells [12,13]. LPS is a unique lysoPL that stimulates mast-cell degranulation, leading to the histamine release from these cells [14,15].
The intracellular synthesis and transport of lysoPLs, especially LPA, are well documented [8,16]. Inside the cell, lysoPLs are generally believed to be transported by FA-binding protein. LysoPLs are also found in the extracellular space. For example, several cell types, including activated platelets or adipocytes, are known to produce LPA . LPC with a C16:0 acyl chain was found to be the most abundant LPC in plasma . Furthermore, the sites at which lysoPLs were detected in previous studies were not always coincident with the expected target tissues and cells. For example, LPE is released from cultured hepatocytes  and accumulates in serum  and ischaemic heart . However, not much is known about the transport of lysoPLs in the extracellular space. A likely binding protein for serum lysoPLs that can facilitate the transport of these hydrophobic moities is HSA (human serum albumin) , which is generally regarded as the major lipid-binding protein in plasma.
HSA is the most abundant protein (∼0.64 mM) in human serum  and accounts for 50–60%  of total plasma protein. Its physiological and pharmacological properties have been extensively studied over several decades. One of the well-established physiological roles of HSA is to transport several endogenous compounds (e.g. FAs and bilirubin ) and some exogenous ligands (e.g. drugs). The first crystal structure of HSA at low resolution (3.1 Å; 1 Å=0.1 nm) was originally reported by Carter and co-workers in 1989 [26–28]. Later, a much higher resolution (2.5 Å) structure of HSA was published by another research group . The crystallographic analysis revealed that HSA is composed of 585 amino acid residues with three similar α-helical domains (I, II and III), each containing two subdomains (A and B), and the whole protein is stabilized by 17 disulfide bonds. In recent years, a number of crystal structures of HSA in complex with one ligand (e.g. ) or up to three ligands (e.g. ) were determined. These structural studies not only localized the two primary ligand-binding sites, Sudlow site 1 and site 2 [31a] to subdomain IIA and subdomain IIIA, but also identified new drug-binding sites. For example, we reported the new drug-binding subsite in Sudlow site I  and therefore showed that Sudlow site I can be further divided into three subsites. Under physiological conditions, each HSA molecule can bind 0.1–2 molecules of FA, but, in certain disease states or after exercise or adrenergic stimulation the molar ratio of FA to HSA can rise to much higher levels . HSA was found to bind to lysoPLs . This led us to question whether the binding of FA to HSA affects the binding of lysoPL to HSA.
In the present study we demonstrated that one of the lysoPLs, LPE, binds to HSA with a dissociation constant of 5.6±1.1 μM. We also determined the crystal structure of HSA in complex with both FA [as Myr (sodium myristate)] and LPE, which showed that LPE binds at Sudlow site I located in subdomain IIA. This study sheds light on structural information on the HSA–lysoPL interaction and may facilitate our understanding of the transport and distribution of lysoPLs.
MATERIALS AND METHODS
FA-free HSA was purchased from Sigma–Aldrich and was used without further purification . L-α-LPE was purchased from Avanti Polar Lipids and was dissolved in DMSO before use. Myr was purchased from Sigma–Aldrich. Ultra-pure water was prepared using a Millipore Milli-Q water-purification. Other chemicals used were of analytical grade and purchased from Shanghai Reagents, China.
Fluorescence-spectroscopy measurements of the HSA–LPE interaction
Fluorescence experiments were carried out on a Varian Eclipse spectrofluorimeter equipped with a xenon lamp source and 1.0- cm-path-length quartz cells. The interaction of LPE with HSA was monitored by recording the quenching of the HSA intrinsic tryptophan fluorescence upon the addition of LPE. The excitation slit and the emission bandwidths were both 5 nm, and the excitation and emission wavelengths were set at 282 and 342 nm respectively. HSA was prepared with a dilution buffer (85 mM phosphate buffer, pH7.5) to the final concentration of 1.0 μM for fluorescence-quenching experiments. LPE was dissolved in DMSO. Titrations were carried out at room temperature (25 °C). The fluorescence intensities at different concentrations of quencher were corrected for the buffer contribution before plotting and further analysis. The affinity was estimated by plotting the decrease of fluorescence intensity at the emission maximum as (Fi–Fmin)/(F0–Fmin) against the quencher concentration. F0 is the maximum fluorescence intensity of the protein alone, Fi is the fluorescence intensity after the ith addition of quencher and Fmin is the fluorescence intensity at a saturating concentration of quencher. The binding data derived from changes in protein fluorescence were fitted to a hyperbolic equation by non-linear regression  using software Origin 7.0: where Bmax is the calculated maximal binding, X is the quencher concentration in μM, Y is the relative reduction of fluorescence intensity at the emission maximum as (Fi − Fmin)/(F0 − Fmin) upon addition of the quencher, and Kd is the calculated dissociation constant in μM.
The effect of FA on the interaction between HSA and LPE was also studied. We measured the HSA fluorescence quenching induced by LPE in the presence of Myr at HSA/Myr molar ratios of either 1:2 or 1:7.
Preparation and crystallization of the HSA–Myr–LPE complex
For crystallization, the preparation of HSA and Myr solution was as described previously [32,35]. The HSA–Myr–LPE complex was prepared in molar proportions of 1:7:7 and then incubated overnight at 50 °C. Excess and/or unbound Myr was removed by centrifugation at 12000 g for 4 min. Samples of the HSA–Myr–LPE complex were concentrated using an Amicon centrifugal concentrator with a 30 kDa molecular-mass cut-off to a final concentration of about 100 mg/ml. The material was then stored at −80 °C before use.
The HSA–Myr–LPE complex was crystallized by the conventional sitting-drop vapour-diffusion method at room temperature. The HSA–Myr–LPE complex (2.0 μl) was mixed with an equal volume of the reservoir solution consisting of 32% (w/v) poly(ethylene glycol) 3350, 85 mM potassium phosphate, pH 7.5, and 5 mM sodium azide. Crystals grew spontaneously as clusters of rods in about 3–4 days. The streak-seeding method was used to obtain the crystals used for diffraction [35a].
X-ray data collection and structure determination
X-ray diffraction data were collected at 100 K on the APS SERCAT (Advanced Photon Source, Southeastern Regional Collaborative Access Team) beamline 22-ID at the Argonne National Laboratory, Chicago, IL, U.S.A. HSA crystals tend to lose their X-ray diffraction capacity at low temperature. We have found that the following cryoprotectant freezes HSA crystals to 100 K and maintains their X-ray diffraction capacity: 32% (w/v) poly(ethylene glycol) 3350, 85 mM potassium phosphate, pH 7.5, and 5% DMSO. We typically soaked our crystal briefly in this cryoprotectant solution and then froze the crystal in a liquid-nitrogen stream on an X-ray beamline. The diffraction data were indexed and processed using the HKL2000 program. The crystal structure of the HSA–Myr–LPE complex was solved by molecular replacement with the AMORE program , using the defatted HSA co-ordinates (PDB code 1N5U ) stripped of its ligands as a model to minimize model bias. A composite and σ-weighted 2Fobs–Fcalc omit map  was used throughout this work (where Fobs and Fcalc are the observed and calculated structure factors respectively). An electron-density map calculated after the molecular-replacement stage showed clear electron density for LPE and Myr ligands. Manual adjustment by the Coot (Crystallographic Object-Oriented Toolkit) program  was used prior to each round of positional refinement by REFMAC of CCP4i . After several rounds of manual adjustments and refinements, TLS (translation/libration/screw) refinement , where HSA was separated into six TLS groups for each subdomain , was carried out in REFMAC (version 5.2) as the last step of refinement. Data collection and final refinement statistics are summarized in Table 1. Figures depicting the structure were prepared by PyMOL (DeLano Scientific; http://www.pymol.org). The atomic co-ordinates for HSA–Myr–LPE were deposited in the PDB under the code 3CX9.
LPE-induced HSA tryptophan fluorescence quenching
Fluorescence spectroscopy has been widely used owing to its exceptional sensitivity, selectivity, convenience and abundant theoretical foundation . HSA is particularly amenable to study by fluorescent quenching because it contains only one tryptophan residue, which has been used extensively as a fluorescent reporter group for ligand binding and conformational studies . In this case, the fluorescence intensity of HSA decreased with the increase of LPE concentration (Figure 2). In the absence of Myr, the HSA fluorescence intensity reached a steady state at an LPE/HSA molar ratio of 20 (Figure 2). The fluorescence-quenching data was found to fit well to a single-binding-site model (eqn 1 and Figure 3), yielding the dissociation constants (Kd) for the HSA–LPE complex of 5.6 μM in the absence of Myr and 12.9 μM in the presence of 2 M Myr. These binding affinities are comparable with the reported values for similar lysoPLs, including oleoyl-LPC , oleoyl-LPE  and dansyl [N-(5-dimethylaminonaphthalenesulphonyl)]-LPE . HSA typically can bind up to seven FAs . Consistent with this finding, we observed no significant LPE-induced fluorescence quenching in the presence of 7 mol-equiv. of Myr.
Crystal structure of the HSA–Myr–LPE complex
In human plasma, HSA was found to bind to FA to some degree, depending on the physiological and disease state [24,45]. In the present study we crystallized HSA in the presence of Myr, partly to simulate physiological conditions, but also to stabilize the protein against denaturation [46,47], thereby facilitating crystal formation and improving the quality of crystals in order to obtain higher-resolution diffraction data [32,35,48]. The initial crystals of the HSA–Myr–LPE complex were formed using co-crystallization, and, after several rounds of streak seeding, the crystals diffracted to 2.8 Å. The structure was determined by the molecular-replacement method. The electron-density map (2Fobs–Fcalc σ-weighted omit map; Figure 5A) in Sudlow site I in domain IIA showed a electron density that was much larger than that typically observed for Myr, which was then modelled with confidence to an LPE molecule (Figure 5D). Five FAs (Myr) were also built into the electron-density map. The small sizes of the electron densities in these FA sites seem to suggest that they were unlikely to be LPE. Thus only one LPE molecule and five Myr molecules were included in the final model. This final model (Figure 4) was refined to an R value of 0.224, an Rfree value of 0.296 (Table 1) and a satisfactory stereochemistry with 90.3% residues in the most favoured region and 8.6% in the additional allowed region in the Ramachandran plot. The rmsds (root mean square deviations) of bond length and bond angles were 0.014 Å and 1.524° respectively (Table 1). The Myr molecules identified from this structure correspond to the FA site 2, 3, 4, 5 and 6 in the previous HSA structure 1BJ5 . No electron density was observed in the FA site 1 located in subdomain IB, consistent with the proposal that this site is a weak FA-binding site [24,49].
Our crystal structure of the HSA–Myr–LPE complex strongly suggested the existence of only one LPE molecule in HSA in the presence of Myr. This LPE occupies Sudlow site I in the domain IIA of HSA. Sudlow site I is a large drug-binding site that can be further divided into three subsites : an FA7 subsite (occupied by FA 7; also called the ‘salicylic acid subsite’), an indomethacin subsite and an AZT (3′-azido-3′-deoxythymidine) subsite (Figure 5C). The FA7 subsite located at the bottom of Sudlow site I is hydrophobic in nature. This subsite is commonly occupied by an FA in the HSA–FA complex [44,50,51]. The FA binding at this subsite seemed to be weak, because it was readily displaced by many drugs, including warfarin , phenylbutazone , azapropazone  and aspirin . In contrast with this, not many instances were found for the occupation of the indomethacin subsite and AZT subsite. The AZT subsite was located at the entrance of Sudlow site I and was close to subdomain IB. There was no overlap among these three subsites (Figure 5C). In the present study we found that LPE occupies the FA7 subsite and part of the AZT subsite, but not the indomethacin subsite (Figure 5C).
LPE binding to HSA
PE (phosphatidylethanolamine) is a phospholipid with two FA moieties. The removal of one FA from PE by the enzyme phospholipase A2 yields LPE . LPE can be found in small amounts in human plasma, in plant and animal tissue, being especially rich in egg yolk and brain tissue . The extracellular transport mechanism of LPE is unknown. HSA is a major component of plasma protein. One of the primary roles of albumin is to transport FAs . HSA binds to 0.1–2 molecules of FA under physiological conditions  and can bind up to seven FAs under certain disease states or after exercise or adrenergic stimulation . The dissociation constants of FA to HSA range from 0.048 μM to 21 μM [44,53]. Up to ten FA-binding sites on HSA have been defined [44,48,50]. FAs with the longer acyl chain usually bind more strongly to HSA [46,54]. The acyl chain of LPE is the same length as the FA palmitate. Thus, it is possible that LPE may be transported by HSA.
We showed in the present work, by fluorescence quenching, that HSA binds to LPE with a dissociation constant of 5.6 μM. This binding is consistent with that observed in a previous study, where the dissociation constant between HSA and fluorescently labelled dansyl-LPE was reported to be in the micromolar range . In the absence of FA, HSA may bind to several LPE molecules, and thus the binding affinity we observed probably represents an average value. In the presence of 2 mol-equiv. of Myr, HSA binds LPE with a lower affinity (Kd of 12.9 μM), measured in the fluorescence-quenching assay. In the presence of larger amount of Myr (HSA/Myr=1:7), no more LPE-induced HSA fluorescence quenching was observed, consistent with observations that HSA typically binds to seven FAs with medium or long chain lengths . These results suggest that FA may function as a regulator for the transport or binding of LPE by HSA in vivo. Consistent with this, Ojala et al.  found that albumin can scavenge LPC's toxic effect on human neutrophils, but that such an effect can be abolished in the presence of a 5-fold molar excess of stearic acid.
Structural basis for the molecular interaction between LPE and HSA
We obtained the crystal structure of HSA in complex with one of the lysoPLs, namely LPE, permitting us to study the molecular interaction between HSA and LPE. Our structural study indicates the acyl chain of LPE occupies the FA7 subsite of Sudlow site I of HSA. The FA7 subsite of Sudlow site I is quite hydrophobic in nature compared with the other FA subsites and is formed by the residues Leu219, Phe223, Leu234, Leu238, Val241, Leu260, Ile264, Ile290 and Ala291. The opening of this hydrophobic subsite is defined by residues Leu219, Leu238, Val241 and Ala291. Sudlow site I has a preference for the binding of large heterocyclic and negatively charged drug compounds, e.g. salicylic acid , warfarin , 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, oxyphenbutazone and phenylbutazone . The planar heterocyclic rings of these drug compounds are pinned snugly between residues Leu238 and Ala291 . In the case of the HSA–Myr–LPE complex, LPE interacts with HSA residues Arg257, His242, Leu238, Ala291, Arg222, Tyr150, Leu260, Ile290, Cys245, Val241, Gln196, Leu219, Glu153, Ser287, Trp214 and Lys199 (ordered by their contact surface area to LPE; Figure 5D). The binding mode of the LPE acyl chain inside HSA is quite similar to the binding mode of Myr in this subsite. In fact, the structures of the acyl chains of LPE and Myr at the FA7 site (in PDB code 1E7G ) are superimposable.
Whereas the acyl chain of LPE occupies the FA7 subsite of Sudlow site 1, the polar head group of LPE occupies the AZT subsite (Figure 5C). The polar head of LPE interacts with the HSA polar residues Arg257, His242, Ala291, Tyr150, Cys235, Val241, Gln196, Glu153 and Ser287 (ranked by the contact surface area between HSA and LPE). Of them, Arg257 has a large contact surface area (46 Å2 or 28% of its exposed area), hydrogen-bonds to LPE and is located near the phosphate and glycine headgroup of LPE, and thus may be important for the positioning of LPE in Sudlow site I (Figure 5D). Residues Glu153 and Glu196 are located at the opening of Sudlow site I and may interact with the ethanolamine headgroup of LPE (Figure 5D). It is noteworthy that the polar headgroup of LPE does not occupy the whole AZT subsite (Figure 5C), indicating that this subsite has the capacity to accommodate a bigger polar group. This location of the LPE headgroup also explains that a fluorescent LPE, namely dansyl-LPE, can be accommodated at this same pocket of HSA . Taken together, although the acyl chain of LPE inserts inside Sudlow site I, its headgroup remains at the Sudlow site I entrance region (AZT subsite; Figure 5B) and is partially exposed to solvent, consistent with the chemically polar nature of the LPE headgroup.
It was observed that Myr binding to HSA has varied affinities (dissociation constants of 0.048–21 μM [44,53]) that depend on the extents of FA binding. Myr at Sudlow site I (FA7) has the weakest binding to HSA [24,49], and Myr at this site is often displaced by many drugs, including warfarin , phenylbutazone , azapropazone  and aspirin . In the present study we mixed HSA with Myr and LPE during our crystallization trial. We found five Myr molecules on HSA, but only one LPE can be clearly identified at Sudlow site I. It is possible that LPE has a stronger binding affinity than Myr at this site and thus can replace it. The fact that circulating HSA typically contains two FA molecules seems to support the physiological relevance of the currently determined HSA–Myr–LPE structure. However, it should be pointed out that the current structure has limited resolution, as in the cases of most HSA crystal structures. Even though we can identify, with confidence, one LPE molecule at Sudlow site I in the current structure, there is a possibility of more than one LPE-binding site on HSA, because the flexibility of FA and lysoPL acyl chains and the limited resolution of the current structure prevent us clearly distinguishing between Myr and potentially disordered lysoPL on the basis of the size of their electron density.
Both the indomethacin subsite and the AZT subsite are quite polar in nature and are partially exposed to solvent. The LPE headgroup occupies only the AZT subsite, leaving the indomethacin subsite empty, despite the relatively large size of LPE in comparison with Myr. This likely reflects the fact that the AZT subsite is slightly more solvent-exposed than the indomethacin subsite.
Does the binding of LPE cause a conformational change in HSA?
The present study shows that LPE can bind to, and thus be transported by, HSA. However, LPE is a larger molecule than FAs, the common HSA endogenous ligand. Does the binding of LPE to HSA cause a conformational change and perturb the overall or local structure of HSA? It was previously established that FA binding to HSA can cause considerable conformational changes to HSA, including expanding the size of Sudlow site I . The existence of an AZT subsite in Sudlow site I depends on the presence of Myr . In the absence of Myr, the side chain of Tyr150 projects into Sudlow site I and overlaps with the AZT-binding subsite . Myr binding to HSA induces a substantial conformational change in HSA involving rotations of domains I and III relative to domain II. A Myr molecule (Myr2) forms a hydrogen-bond with the Tyr150 side chain, leading to the re-orientation of the side chain of Tyr150 outside of Sudlow site I, thus generating the AZT subsite. The present structural study shows no global change in the HSA structure compared with the structure of the HSA–Myr complex (PDB code 1E7G ).
Can HSA bind to other phospholipids?
We showed that LPE occupies subsite FA7 and part of subsite AZT of HSA Sudlow site I. The acyl chain of LPE occupies the whole FA7 subsite, whereas the polar head group of LPE just stretches to the AZT subsite, which is at the entrance of Sudlow site I and near the solvent (Figure 5B). On the basis of this localization of LPE, it can be expected that Sudlow site I is capable of accommodating other lysoPLs, including LPC and LPS (Figure 1). However, this conclusion awaits further experimental verification.
The Sudlow site I is quite large in size. LPE occupies only the FA7 part of the AZT subsite and leaves the indomethacin site empty. Is the Sudlow site 1 large enough to accommodate regular phospholipids with two acyl chains? We carried out a preliminary modelling study based on the current HSA–LPE structure. The result suggests that the indomethacin subsite has the proper size and right orientation to accommodate the second acyl chain of a phospholipid molecule. A recent report showed that HSA indeed binds to a phospholipid (dioleoyl-PE), albeit with weaker binding affinity (4.7×103 M−1 ) compared with FAs. It will be interesting to see how HSA accommodates structurally such molecules that are much larger than FAs.
In summary, we have demonstrated that one molecule of HSA can bind one LPE molecule, even in the presence of FAs, despite the relatively large size of this lysoPL. The binding affinity between LPE and HSA is comparable with that of FAs. Moreover, we showed that LPE locates at subdomain IIA of HSA and occupies two of three subsites in Sudlow site I. The LPE acyl chain occupies the hydrophobic bottom of Sudlow site I, whereas the polar headgroup locates at the Sudlow site I entrance region pointing towards the solvent. Taken together, these results demonstrate that HSA is capable of transporting LPE. Our structural information also predicts that HSA may be able to transport other kinds of lysoPLs.
Shihui Guo carried out the experiments and wrote the initial draft of the manuscript. Feng Yang helped in protein crystallization. Liqing Chen and Edward J. Meehan collected the X-ray data. Chuanbing Bian helped in structural determination. Xiaoli Shi helped in manuscript preparation. Mingdong Huang designed the project and wrote/revised the manuscript.
This work was supported by the Chinese Academy of Sciences [grant number KSCX2-YW-R-082]; the National Natural Science Foundation of China [grant numbers 30800181, 30625011]; the Ministry of Science and Technology (China) [grant numbers 2007CB914304, 2006AA02A313]; the National Science Foundation Experimental Program to Stimulate Competitive Research (U.S.A.); and the US Department of Energy, Office of Science, Office of Basic Energy Sciences (use of the APS under contract no. W-31-109-Eng-38).
We thank the staff of the APS SERCAT beamline 22-ID for help with data collection.
The atomic co-ordinates for human serum albumin in complex with myristic acid and lysophosphatidylethanolamine have been deposited in the PDB under the code 3CX9.
Abbreviations: APS SERCAT, Advanced Photon Source, Southeastern Regional Collaborative Access Team; AZT, 3′-azido-3′-deoxythymidine; dansyl, N-(5-dimethylaminonaphthalenesulphonyl); FA, fatty acid; HSA, human serum albumin; LPA, lysophosphatidic acid; LPC, lysophosphatidylcholine; LPE, lysophosphatidylethanolamine; LPG, lysophosphatidylglycerol; lysoPL, lysophospholipid; LPS, lysophosphatidylserine; Myr, sodium myristate; PE, phosphatidylethanolamine; rmsd, root mean square deviation; TLS, translation/libration/screw
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