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The KWS‐1 small‐angle neutron scattering (SANS) instrument operated by the Jülich Centre for Neutron Science (JCNS) at the research reactor FRM II of the Heinz Maier‐Leibnitz Zentrum in Garching near Munich has been recently upgraded. The KWS‐1 instrument was updated, from its active collimation apertures to the detector cabling. Most of the parts of the instrument were installed for the first time, including a broadband polarizer, a large‐cross‐section radio‐frequency spin flipper, a chopper and neutron lenses. A custom‐designed hexapod in the sample position allows heavy loads and precise sample positioning in the beam for conventional SANS experiments as well as for grazing‐incidence SANS under applied magnetic field. With the foreseen in situ polarization analysis the main scientific topic of the instrument tends towards magnetism. The performance of the polarizer and flipper was checked with a polarized 3He cell at the sample position. The results of these checks and a comparison of test measurements on a ferrofluid in a magnetic field with polarized and nonpolarized neutrons are presented.

Spherical high density lipoprotein (sHDL), a key player in reverse cholesterol transport and the most abundant form of HDL, is associated with cardiovascular diseases. Small angle neutron scattering with contrast variation was used to determine the solution structure of protein and lipid components of reconstituted sHDL. Apolipoprotein A1, the major protein of sHDL, forms a hollow structure that cradles a central compact lipid core. Three apoA1 chains are arranged within the low resolution structure of the protein component as one of three possible global architectures: (i) a helical dimer with a hairpin (HdHp), (ii) three hairpins (3Hp), or (iii) an integrated trimer (iT) in which the three apoA1 monomers mutually associate over a portion of the sHDL surface. Cross-linking and mass spectrometry analyses help to discriminate among the three molecular models and are most consistent with the HdHp overall architecture of apoA1 within sHDL.Epidemiological studies firmly establish that circulating levels of high density lipoprotein (HDL) cholesterol and apolipoprotein A1 (apoA1), 2 the major protein constituent of HDL particles, are inversely associated with atherosclerotic heart disease risk (1-3). Moreover, genetic studies further confirm a strong mechanistic link between HDL and apoA1 and cardiovascular disease (4 -8). Defined by its buoyant density characteristics, HDL represent a heterogeneous group of particles with varied lipid composition and protein content that participate in diverse biological functions ranging from lipid transport to innate immune functions. For example, HDL serves as an acceptor of cholesterol from peripheral tissue macrophages and promotes lipid transport through delivery of cholesterol to the liver and steroidogenic tissues (9 -11). HDL also mediates systemic anti-inflammatory and anti-oxidant functions (12-14), and HDL-associated proteins can play critical host defense functions (15). ApoA1 represents nearly three-quarters of the protein content of HDL by mass, and it plays a central functional role in facilitating the numerous biological activities of HDL. Typically present at 2-4 molecules/particle depending upon the degree of HDL maturation, apoA1 serves as the fundamental structural element of the particle (16, 17) and is critical for specific interactions with proteins involved in HDL biogenesis (18, 19), maturation and remodeling (20,21), and recognition by target organ receptors (22,23).Because HDL can be generated in a relatively homogenous form, most structural studies of HDL have focused on reconstituted nascent HDL, a particle composed of two molecules of apoA1 associated with phospholipid and free cholesterol (16,17). Early small angle neutron scattering (SANS) and small angle x-ray scattering (SAXS) studies of nascent HDL particles were reported nearly 3 decades ago and are consistent with an outer protein layer relative to a central lipid core (24,25). Current structural models of nascent HDL have an anti-parallel apoA1 chain orientation and posit that the protein exists...

Using polarized neutrons, we have determined phases as well as interference amplitudes for noncyclic spinor evolutions in static magnetic fields. Both these quantities depend on the angle subtended by the neutron spin with the field. This experiment elucidates the subtle, and widely misunderstood, concepts involved. [S0031-9007(98)

The predicted structure and molecular trajectories from over 80 ns molecular dynamics simulation of the solvated double super helix (DSH) model of nascent-high density lipoprotein (HDL) was determined and compared with experimental data on reconstituted nascent HDL obtained from multiple biophysical platforms including small angle neutron scattering (SANS) with contrast variation, hydrogen-deuterium exchange tandem mass spectrometry (H/D-MS/MS), nuclear magnetic resonance spectroscopy (NMR), cross-linking tandem mass spectrometry (MS/MS), fluorescent resonance energy transfer (FRET), electron spin resonance spectroscopy (ESR), and electron microscopy. In general, biophysical constraints experimentally derived from the multiple platforms agree with the same quantities evaluated using the simulation trajectory. Notably, key structural features postulated for the recent DSH model of nascent HDL are retained during the simulation including: 1) the super helical conformation of the anti-parallel apolipoprotein A1 (apoA1) chains; 2) the lipid micellar-pseudolamellar organization; and 3) the solvent exposed Solar Flare loops, proposed sites of interaction with LCAT (lecithin cholesteryl acyltransferase). Analysis of salt bridge persistence during simulation provides insights into structural features of apoA1 that form the backbone of the lipoprotein. The combination of molecular dynamics simulation and experimental data from a broad range of biophysical platforms serves as a powerful approach to study large macromolecular assemblies such as lipoproteins. The present application to nascent HDL validates the DSH model proposed earlier, and suggests new structural details of nascent HDL. 4 To whom correspondence should be addressed: Cleveland State University, 2121 Euclid Avenue, SI 422, Cleveland, OH 44115, or Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, v.gogonea@csuohio.edu or hazens@ccf.org,. SUPPORTING INFORMATION AVAILABLE. The supporting information contains Suplemmental Figures 1 and 2 that depict small angle neutron scattering intensities (I(q)) versus the scattering vector (q), and distance distribution functions (p(r)) versus the distance between scattering centers (r), and low-resolution structures of nascent rHDL in 12% and 42% D 2 O. The Supplemental Table 1 lists experimental and calculated per residue deuterium incorporation factors, H/D exchange rate constants, and residue unfolding constants. This material is available free of charge via the Internet at http://pubs.acs.org. Additionally, the following information is available for download from http://www.lerner.ccf.org/cellbio/hazen/data/ -neutron scattering intensities for HDL samples analyzed in 12% and 42% D 2 O (text files), low resolution structures of nascent HDL (pdb files), and calculated H/D exchange deuterium incorporation factors for all residues in apoA1 dimer (Excel file). NIH Public Access Author ManuscriptBiochemistry. Author manuscript; available in PMC 2011 August 31. NIH-PA Author ManuscriptNIH-PA Author Manuscri...