Abstract

We have identified the fibrin protofibril and studied its structure in electron micrographs of negatively stained specimens. Based on these images and considerations of symmetry we have constructed a model of the protofibril, in which two strands of the trinodular fibrin molecules are related by a two-fold screw axis between the strands and two-fold axes perpendicular to them. The molecules in a strand are joined by longitudinal contacts between outer nodules, and the two strands are held together by a single type of lateral contact between a central nodule on one strand and an outer nodule on the other. This interpretation of the structure of protofibrils is supported by images of trimer complexes, which show a single molecule of one strand attached laterally (by its central nodule) to the outer nodules of two molecules of the other strand. These lateral contacts, which are presumably the site of thrombin activation, are entirely saturated within the protofibril. We conclude that the association of protofibrils to form thicker fibers must involve a second type of lateral contact, probably between outer nodules of adjacent, inregister strands.

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