A PROPOSED STRUCTURAL MODEL OF DOMAIN-1 OF FASCICLIN-III NEURAL CELL-ADHESION PROTEIN-BASED ON AN INVERSE FOLDING ALGORITHM

Fasciclin III is an integral membrane protein expressed on a subset of axons in the developing Drosophila nervous system. It consists of an intracellular domain, a transmembrane region, and an extracellular reg ion composed of three domains, each predicted to form an immunoglobuli n-like fold. The most N-terminal of these domains is expected to be im portant in mediating cell-cell recognition events during nervous syste m development. To learn more about the structure/function relationship s in this cellular recognition molecule, a model structure of this dom ain was built. A sequence-to-structure alignment algorithm was used to align the protein sequence of the fasciclin III first domain to the i mmunoglobulin McPC603 structure. Based on this alignment, a model of t he domain was built using standard homology modeling techniques. Side- chain conformations were automatically modeled using a rotamer search algorithm and the model was minimized to relax atomic overlaps; The re sulting model is compact and has chemical characteristics consistent w ith related globular protein structures. This model is a de novo test of the sequence-to-structure alignment algorithm and is currently bein g used as the basis for mutagenesis experiments to discern the parts o f the fasciclin III protein that are necessary for hemophilic molecula r recognition in the developing Drosophila nervous system.