Immune system features are ubiquitous across living organisms, and regulate host-pathogen or host-symbiont relationships across domains of life. This thesis explores proteins mediating aspects of immunity in four different systems. First, I explore broadly neutralizing antibodies against the SARS-CoV-2 viral entry protein S. I identified the antibody 11G-12v as belonging to Class 1/4. I additionally found that it shares sequence and structural similarity to a set of previously discovered anti-SARS-CoV-2 RBD antibodies that have a long CDRH3 loop with a YYDRxG motif, which associate with and extend the central beta sheet of the SARS-CoV-2 RBD. Second, I examined the many documented activities of the p97 adapter protein Phospholipase A2 Activating protein in the context of its structure, and considered them in terms of pleiotropy, as some of its functions appear to occur without p97. Third, I solved the crystal structure of the autophagy intiation scaffold FIP200's C-terminal CLAW domain in complex with a 13-amino acid phosphopeptide derived from the TNIP1 FIP200 interacting region, or FIR. This crystal structure supported our understanding of the basis of FIR recognition by CLAW. And finally, I collaborated with the Aravin group and solved five cryo-EM structures of RzAgo, a prokaryotic argonaute protein with two unique N terminal domains. We found that RzAgo forms tetramers to assume an active state, which recapitulates structures previously observed in certain structures of homologous mammalian proteins. However, in its inactive state, RzAgo forms filaments that lock its catalytic sites in a non-catalytic organization. Together, this work demonstrates the contributions of structural biology to studying immune system proteins.
Katelyn Margaret Radford (Mon,) studied this question.