The Structure of Human‐Plasma Low‐Density Lipoprotein B

Abstract

1. The X-ray small-angle scattering of human plasma lipoprotein B of the low-density fraction ( Q = 1.016-1.060 g . ~m -~) has been recorded to high precision at different electron density contrasts.2. The overall structure of the particles is characterized by a quasi-spherical shape and radial symmetry. A maximum diameter of 23 nm and a molecular weight of 2.4 x lo6 have been determined.3. The internal structure is described in terms of a model consisting of spherical layers with different electron densities indicating that the neutral lipids are arranged in the core of the molecule up to a radius of about 8 nm surrounded by a monolayer of free cholesterol, phospholipids and protein. The neutral lipids are shown to be in an ordered, liquid crystalline state at 4 "C and to undergo a thermotropic transition into a disordered state at higher temperatures.Low-density lipoproteins play a central role in lipid metabolism as the major transport vehicles of cholesterol in the human organism [1,2]. Their apparent pathophysiological significance in the development of atherosclerosis [3 -51 underlines the need for a thorough characterization of this macromolecular 1ipid.protein complex to provide a basis for the establishment of structure-function relationships.Numerous physico-chemical studies (for recent reviews see [6 -91) have led to the generally accepted idea that low-density lipoproteins form highly isotropic, sphere-like particles of about 22-nm diameter. More controversial are the current ideas with respect to the internal structure of low-density lipoproteins. In attempts to define the spatial relationship of the individual lipid and the protein constituents within the complex. various techniques have been applied and the results provided a wealth of information about the microenvironment of the molecular components. However, they are difficult to integrate into one consistent model of the molecular architecture of lowdensity lipoprotein without resorting to speculation.The method of X-ray small-angle scattering [lo, 1 I ] in principle provides both information on the overall shape of particles as well as their internal structure when the scattering functions are recorded at different electron density contrasts [12]. From the fact that lowdensity lipoproteins are macromolecular complexes consisting of discrete molecular components of different electron densities the scattering information is highly complex and not easily interpreted unequivocally; all the former X-ray studies [13 -151 on lowdensity lipoprotein structure have introduced certain a priori assumptions in the data analysis with respect to either, the 'allowed' electron density levels within the particles [15] or the overall shape [14]. By adopting a suitable set of theoretical considerations and conditions [16] Tardicu et al. arrived at a quasispherical structure of low-density lipoprotein [15,17], in which the surface shows convolutions between long spikes (8 nm). A maximum diameter of 29 nm and a solvent penetration reaching to 5.5 nm far from t...

One site on the apoB‐100 specifically binds 17‐β‐estradiol and regulates the overall structure of LDL

“…The present technology in synchrotron X-ray scattering allows the achievement of highly defined data on dilute particles. As for experiments on LDL particles, X-ray scattering can monitor the structure of the lipid core, of the interfacial shell, and of the protein and phospholipid head groups surface shell (19)(20), without radiation damage effects (21). In Fig.…”

Assembly of Lipoprotein Particles Containing Apolipoprotein-B: Structural Model for the Nascent Lipoprotein Particle

“…Experimental evidence and theoretical predictions have offered insights into the structure of apoB and the apoB lipoprotein particles. Early work using calorimetry and x-ray diffraction (Atkinson et al, 1977;Deckelbaum et al, 1977Deckelbaum et al, , 1975Muller et al, 1978), and more recently cryo-electron microscopy (Chatterton et al, 1995a(Chatterton et al, ,b, 1991Gantz et al, 2000;Spin and Atkinson, 1995;van Antwerpen et al, 1997van Antwerpen et al, , 1999, indicated that apoB is located on the surface of a spheroidal lipoprotein particle.…”

High hydrostatic pressure specifically affects molecular dynamics and shape of low-density lipoprotein particles

“…We applied HHP to compare the dynamical behaviour of LDL particles with a healthy normolipidemic composition (N-LDL) to a triglyceride-rich form of LDL (TG-LDL), which mimics pathologically modified LDL. The chemical compositions of LDL particles are well described in the literature2345. Each particle (Fig.…”