A MODEL OF INSULIN FIBRILS DERIVED FROM THE X-RAY CRYSTAL-STRUCTURE OF A MONOMERIC INSULIN (DESPENTAPEPTIDE INSULIN)

The crystal structure of despentapeptide insulin, a monomeric insulin, has been refined at 1.3 Angstrom spacing and subsequently used to pre dict and model the organization in the insulin fibril. The model makes use of the contacts in the densely packed despentapeptide insulin cry stal, and takes into account other experimental evidence, including bi nding studies with Congo red. The dimensions of this model fibril corr espond well with those measured experimentally, and the monomer-monome r contacts within the fibril are in accordance with the known physical chemistry of insulin fibrils. Using this model, it may be possible to predict mutations in insulin that might alleviate problems associated with fibril formation during insulin therapy. (C) 1997 Wiley-Liss, In c.