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J W Weisel

Publications and source records attributed to J W Weisel.

65 records · Page 4Linked to original sources
PubMed1983

The structure of fibrinogen and fibrin: II. Architecture of the fibrin clot.

Our present low resolution model for fibrinogen based on electron microscopy and x-ray diffraction data has been described by Cohen et al. A unique aspect of the structural analysis of fibrous proteins is that the molecular packing in ordered arrays reflects biologically significant intermolecular interactions. We have shown that the orthogonal sheet microcrystals, which are closely related to fibrin, are made up of a highly regular arrangement of two-stranded protofibrils, and we have visualized aspects of both the substructure of the protofibrils as well as their packing to form the fibrin clot. By correlation of structural data with biochemical studies we have begun to identify certain functional regions of the fibrinogen model related to fibrin. Many aspects of fibrinogen's physiological activity remain to be related to its structure. As our present model is improved by higher resolution studies, we will see with increasing clarity molecular features critical for clot formation and fibrinolysis.

Computers↗
PubMed1983

Xenopus fibrinogen. Characterization of subunits and hormonal regulation of biosynthesis.

In this paper we describe the purification and characterization of Xenopus plasma fibrinogen and the hormonal factors which regulate synthesis and secretion of fibrinogen in liver parenchymal cells in primary culture. As in other vertebrate species, Xenopus fibrinogen is composed of three nonidentical polypeptide chains, A alpha, B beta, and gamma. In contrast to mammalian fibrinogens, the B beta chain of Xenopus fibrinogen has a higher apparent molecular weight than the A alpha chain. The gamma chain has the lowest molecular weight in the frog protein, as in that of other species. The relatively large size of the frog B beta chain results from the unusually large size of the NH2-terminal B fibrinopeptide, which is released by thrombin cleavage of fibrinogen. Hormonal regulation of fibrinogen biosynthesis was examined using a primary cell culture system. Purified Xenopus liver parenchymal cells, maintained for several weeks in a defined culture medium, gradually decrease the synthesis and secretion of fibrinogen. Sustained production of this protein is dependent upon the addition of a glucocorticoid, dexamethasone, to the culture medium. Fibrinogen production is suppressed if an estrogen, estradiol-17 beta, is added to the culture medium together with dexamethasone and triiodothyronine. The Xenopus system provides new insight into the structure of fibrinogen, the evolution of this protein, and the hormonal factors which regulate its synthesis.

Animals↗
PubMedDate not supplied

The electron microscope band pattern of human fibrin: various stains, lateral order, and carbohydrate localization.

Human fibrin negatively contrasted with a variety of heavy metal compounds and examined by electron microscopy displays a distinctive, nonpolar band pattern with a repeat of 22.5 nm. These results together with a reversal of contrast observed in images of positively stained fibrin, indicate that the striations reflect the protein density along the fiber. All major features of the band pattern can be accounted for directly in terms of a model for the structure of fibrinogen. Optical and computed diffraction patterns of micrographs of fibrin show that most specimens are highly ordered along the fiber axis but have only diffuse equatorial reflections arising from the average spacing of the protofibrils, although occasional fibers have discrete reflections at about 19 nm. Finally, the resulting change in negative staining pattern upon binding of lectins to the carbohydrate moieties is distinctive and allows the carbohydrate-containing beta domain of the molecule to be localized.

Fibrin↗