Our experiment was built upon previous studies which found a correlation between the ErbB4 pathway and amyotrophic lateral sclerosis. Using computational methods such as sequence alignment and secondary structure prediction, we identified two possible TACE cleavage sites on the ErbB4 protein, which was previously unknown. These two possible cleavage sites, located at amino acids 651-659 (PLIAAGVIG) and 1073-1078 (AEQGVS) respectively, were found to be significantly far away from the two ALS-associated mutations at codons 927 and 1275. Although we were unable to visualize the second mutation and second possible cleavage site in PyMOL (since that region of ErbB4 was not available in the RCSB Protein Databank), we know that they were too far apart to have any kind of proteolytic impact on one another. Therefore, we can make the plausible assumption that the mutations will not impact TACE's cleavage of ErbB4, at least not at the cleavage sites we have identified.

Although our project has determined that the ALS-associated mutations do not impact ErbB4's proteolysis by TACE, we have still provided valuable knowledge to the scientific community. Our results indicate that the two mutations we investigated likely do not affect ErbB4's proteolysis by TACE; however, since the mutations are ALS-associated, there must be some other mechanism within the ErbB4 pathway which is impacted. We have successfully eliminated one possible factor in the ErbB4-ALS pathway and narrowed down the sphere of investigation for future research.