The structure of the chromatin core particle in solution

Pardon, J. F.; Worcester, David L.; Wooley, John; Cotter, Rosalind I.; Lilley, David M.J.; Richards, B. M.

doi:10.1093/nar/4.9.3199

Cited by 123 publications

(51 citation statements)

References 36 publications

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“…The particle is described as a flat cylinder 110 A in diameter and 0 57 A in height. A similar shape and dimensions were found to be consistent 2,3 with the low angle neutron scattering from core particles in solution…”

Section: Introductionsupporting

confidence: 68%

Low resolution models of self-assembled histone fibers from X-ray diffraction studies

Wachtel

Sperling

1979

Nucl Acids Res

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X-ray diffraction data from self-assembled histone fibers are presented for three systems: H4, H3-H4, and the four core histones H2A, H2B, H3 and H4. These data have been obtained under conditions of high ionic strength and high protein concentration which are thought to promote histone conformation similar to that found in intact chromatin. The low angle equatorial scattering (R<,05 A ) is analysed, and, with additional constraints imposed by electron microscopy data, four low resolution fibrillar models are derived. Two features common so all the possible models are a maximum outer iameter of approximately 60 A and a subfibril diameter of approximately 25 A. It is the interference of the Rrotein subfibrils across a central region of low electron-density -a 10 R "hole" -which gives rise to the characteristic diffraction peak at 36 A. Possible relationships of the models of the histone fibers to the structure of the histone component of chromatin are suggested. I NTRODUCT I ONRecently, a low resolution model of the chromatin "core" particle, consisting of 140 base pairs of DNA and eight histones, has been derived from a combination of single crystal X-ray diffraction and electron microscopy data1. The particle is described as a flat cylinder 110 A in diameter and 0 57 A in height. A similar shape and dimensions were found to be consistent 2,3with the low angle neutron scattering from core particles in solutionThe neutron experiments furthermore determined that the bulk of the histone proteins occupies the central region of the particle to a radius of approximately 32 A and that the DNA is supercoiled on the outside. Some conclusions may be drawn concerning the conformation of the DNA. Presumably the strong 28 A periodicity apparent in the crystal data corresponds to the pitch of the DNA superhelix wound about the histone core,

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Section: Introductionsupporting

confidence: 68%

Low resolution models of self-assembled histone fibers from X-ray diffraction studies

Wachtel

Sperling

1979

Nucl Acids Res

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“…SANS with contrast variation, especially when coupled with selective deuteration of individual components, can facilitate triangulation of the location of individual components within macromolecular complexes. For example, SANS with contrast variation was the first method to correctly predict the subunit organization of eukaryotic chromosomes (55), the structural orientation of protein and DNA within the nucleosome (56), and the organization of rhodopsin within retinal rod outer segment (57), as well as to triangulate the location of various proteins and RNA within the ribosome (58,59). Herein we use the combination of contrast variation SANS and selective deuteration of apoA1 to directly visualize the low resolution structure of the protein and lipid core components individually within biologically active reconstituted sHDL.…”

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confidence: 99%

The Low Resolution Structure of ApoA1 in Spherical High Density Lipoprotein Revealed by Small Angle Neutron Scattering

Wu¹,

Gogonea

Lee³

et al. 2011

Journal of Biological Chemistry

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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...

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“…We believe however, that the structures of both the histone octamer and the nucleosome need to be accurately determined. 5,6, and 7 in (1)], which incidently are neutron diffraction studies, as providing firm data against our structure. However, Braddock et al found that the pitch of the DNA superhelix in the nucleosome was 37A.…”

mentioning

confidence: 58%

“…All the same, Burlingame et al argue that their structure for the isolated histone octamer is more relevant to the structure of chromatin than that of the octamer within nucleosome core particles, and go on to propose a different model for the way in which DNA associates with the octamer to form a nucleosome. Their analysis has led to a hydrated spongelike structure and a shape for the octamer which disagrees with the results of x-ray solution scattering on both the octamer and nucleosome core particles (5)(6)(7), and which cannot be fitted into the lattice of nucleosome core crystals. These large discrepancies suggest that the structure proposed by Burlingame et (3).…”

mentioning

confidence: 77%