Receptors for neurotrophins and tumor necrosis factor-like ligands have a variety of functions in cells. These functions include stimulation of growth and differentiation, protection against apoptosis, and induction of apoptosis (programmed cell death). None of these receptors has catalytic activity, so all must transduce signals by recruitment of cytoplasmic signaling proteins. Identifying sites of protein-protein interaction is a complex problem. I have approached this problem by first sorting known members of the family into subgroups based on biological function. This work has been facilitated by the increased number of available protein sequences during the last year as a result of work on genome projects. These subgroup sequences are then aligned based on structural criteria. Several techniques are used to define boundaries of potential protein-protein interaction sites, including secondary structure prediction, alignment gaps, and structural domain data from NMR or X-ray structures when available. Computer Graphics Laboratory support has been essential for this continuing project. The Laboratory has provided software support for the MidasPlus program that we use for visualization and some modeling tasks. Their numerous utilities and display tools are also important to this research. Results obtained from this project have guided experimental approaches in my laboratory, and also served as preliminary data for three applications for extramural support.
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