MOLECULAR AGGREGATION OF THE NEUROPHYSINS. John P. Rose and Bi-Cheng Wang, Department of Biochemistry and Molecular Biology University of Georgia, Athens GA 30602, U.S.A.

Bovine neurophysin II has been crystallized in eight distinct crystal forms containing 1, 2, 3, 4, 6 and 12 molecules per asymmetric unit. The mode of molecular aggregation observed in the crystal structures may be paradigms of how the neurophysin-hormone complexes are packaged in the neurosecretory granules (NSG).

The neurophysins (NP) are a family of disulfide rich proteins responsible for the packaging and transport of the posterior pituitary hormones oxytocin (OT) and vasopressin (VP). Two closely related classes of neurophysins are known, one complexed with VP and the other with OT, this association reflecting the synthesis of each hormone and its associated NP via a common precursor.

During transport, the hormone is cleaved from its neurophysin carrier but remains associated with the protein as a non-covalent complex. The neurophysin-hormone complex is then stored in NSG until release into the blood stream. Within the NSG, the NP-hormone complex concentration can be as high as 1000 mg/ml. Although the mode of NP aggregation within the NSG is unknown, it has been postulated based on the high concentrations observed in the NSG that the complexes exist as dimers, higher aggregates, or even amorphous or crystalline precipitates thus the mode of NP association observed in the crystal structures may serve as a model for neurophysin packaging in the NSG's.

An analysis of the common modes of NP aggregation observed in the crystal structures will be presented.

Work supported by NIH grant GM-46828 and resources from the Pittsburgh Supercomputing Center.