Is there structural specificity in the reversible protein aggregates that are stored in secretory granules?

There are several steps that must occur for secretory granules to form: (1) Secretory proteins that make up the dense cores of the granules must be concentrated; (2) membrane proteins necessary for granule function must accumulate in the correct location; and (3) inappropriate membrane proteins and excess membrane must be removed. Reversible aggregation of secretory granule proteins provides a mechanism for concentrating and sorting these proteins. There is specificity in the way secretory granule proteins are treated in cells that make granules. The specificity has been shown in some cases to occur after the aggregation process, so that granules containing different aggregates function differently. An explanation could be that a property of the aggregate, such as a surface motif, might influence the accumulation of membrane proteins necessary for granule function. Such a conclusion implies that the aggregates are not amorphous but have structure. Use of NMR spectroscopy to investigate changes in the environment of amino acid residues in secretory granule proteins as they form oligomers by using 15N relaxation times might provide a means to determine which residues are specifically involved in aggregation.