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Biomedical subjects

D M Engelman

Publications and source records attributed to D M Engelman.

At least 127 records · Page 7Linked to original sources
PubMed1976

Compositional mapping of cholesteryl ester droplets in the fatty streaks of human aorta.

Frozen sections prepared from human aortic tissue containing fatty streak lesions were examined on a thermally controlled stage with a polarizing light microscope. Distinct birefringent droplets, 0.5-5 mum in diameter, were observed, many apparently aggregated into clusters. The clusters were about 20 X 20 mum in diameter (the approximate size of foam cells). Upon being heated, each smectic droplet exhibited a sudden change of birefringence, indicating a change of state. The transition temperatures were compared to assess compositional distributions in the tissue. We found that for 52% of the clusters the standard deviation of the cluster's droplet melting point distribution was less than half that observed in the surrounding microscopic field. If clusters were intracellular lipid inclusions, this observation indicates that the lipid composition within a foam cell is more homogeneous than that of the overall field. However, using statistical methods, we compared droplet melting populations from cluster to cluster and found significant heterogeneity. The observations can be interpreted to suggest that many foam cells modify the cholesteryl ester fatty acid composition of their accumulations be selective uptake, temporal sampling, or chemical reaction. Furthermore, the intercellular heterogeneity suggests that different cells in the lesion may have different metabolic and transport enzyme affinities or be in different states.

Adolescent↗
PubMed1976

Molecular organization of the cholesteryl ester droplets in the fatty streaks of human aorta.

X-ray diffraction patterns from human arterial specimens containing atherosclerotic fatty streak lesions exhibited a single sharp reflection, corresponding to a structural spacing of about 35 A. Specimens without lesions did not. When specimens with fatty streaks were heated, an order-to-disorder phase transition was revealed by the disappearance of the sharp reflection. The transition was thermally reversible and its temperature varied from aorta to aorta over a range from 28 degrees to 42 degrees C. Since cholesteryl ester droplets are a major component of fatty streaks, comparison studies were made of the diffraction behavior from pure cholesteryl esters. We found that the diffraction patterns of the fatty streak material could be accounted for by the organization of the cholesteryl esters into a liquid-crystalline smectic phase that melts from the smectic to a less ordered phase upon heating. When combined with the conclusions of others from polarized light microscopy, our study shows that a droplet in the smectic phase has well-defined concentric layers of lipid molecules. In each layer, the long axes of the molecules have a net radial orientation with respect to the droplet, but the side-to-side organization is disordered. We suggest that the accessibility of portions of the lipids for specific binding to enzymes or transport proteins may be restricted when they are in the smectic state, and that exchange of lipids with surrounding membranes or other potential binding sites may likewise be inhibited. The restriction in the smectic phase should be greater than in the less ordered phases that exist at higher temperatures.

Adolescent↗
PubMed1976

The production of deuterated E. coli.

Our results indicate that the preparation of deuterated macromolecules for neutron scattering from E. coli can be done easily and relatively cheaply. The entry of deuterium into macromolecules of differing species during cell growth can be controlled by varying the D2O content of the medium and the choice of carbon sources, all in minimal medium. Considering the range of deuterations obtainable with simple protonated carbon sources, there seems to be no reason to use deuterated carbon sources except for the rare occasions when a fully deuterated specimen is required.

Acetates↗
PubMed1975

Neutron scattering measurements of separation and shape of proteins in 30S ribosomal subunit of Escherichia coli: S2-S5, S5-S8, S3-S7.

Neutron scattering measurements done on E. coli 30S ribosomal subunit specimens in which specific pairs of proteins were deuterated have enabled us to estimate the distances between the labeled proteins. The distances between centers of gravity of three protein pairs have been determined: S2-S5 (105 A), S3-S7 (115 A), and S5-S8 (35 A). A method for extracting shape information about these proteins from the neutron scattering profiles is demonstrated. The method shows that S5 and S8 are compact and S2 is extended.

Binding Sites↗
PubMed1974

Asymmetry in the 50S ribosomal subunit of Escherichia coli.

A substantial separation of the centers of mass of the protein and RNA portions of the 50S ribosomal subunit has been achieved using neutron scattering. This separation reveals that the subunit has a protein-rich side, a finding which is inconsistent with many models proposed for the structure. By analyzing the variation of the radius of gyration of the subunit under conditions in which the contributions of the protein and RNA were separately enhanced by deuteration and comparing these radii to the undeuterated subunit radius, we have obtained the following values. The radius of gyration of the whole particle is 78.0 +/- 0.95 A, that of the RNA moiety is 72.5 +/- 1.5 A, and that of the protein is 73.4 +/- 2.0 A. These data give a separation of the centers of mass of the RNA and protein distributions of 57.7 +/- 10 A.

Bacterial Proteins↗
PubMed1972

A new method for the determination of biological quarternary structure by neutron scattering.

Determination of quaternary structure by neutron scattering is proposed. The method gives the identity and relative spatial position of each component of a complex, provided that the complex can be obtained in deuterated form and can be reconstituted from its separated parts. If two components are rich in hydrogen and if the rest of the complex is deuterated, the contrast in scattering power permits the measurement of the separation of the pair from an interference cross term. The structure is obtained by triangulation from a set of measured pair separations.

Deuterium↗