Melissa Call-Projects

Melissa Call-Projects

Projects

T cell receptor structure and function

The T cell antigen receptor  (TCR) recognizes peptide fragments bound to major histocompatibility complex (MHC) proteins, activating T cells to kill target cells and/or secrete soluble factors. While the structural determinants of ligand discrimination are well studied, the mechanism by which receptor engagement outside the cell is sensed by signalling molecules inside the cell is still an open question. We are combining disulphide mapping and solution NMR techniques to determine how the eight-subunit receptor complex is arranged within the membrane and how transmembrane structure and dynamics relate to receptor activation. 

Team member: Logesvaran Krshnan

Regulation of cell-surface immune-regulatory proteins by MARCH-family e3 ubiquitin ligases

The levels of peptide:MHC complexes and other immunologically relevant proteins available at the cell surface can be modulated by regulatory proteins of the Membrane-Associated RING-CH (MARCH) family. MARCHs are integral membrane proteins with alpha-helical TM domains and cytosolic ubiquitin ligase domains. We use cellular biochemical and flow-cytometry based functional assays combined with solution NMR and lipidic cubic phase (LCP) crystallography techniques to study how MARCH proteins trap substrates through interactions with their TM domains. The major aim of this project is to identify what structural motifs govern substrate identification and thereby identify new substrates and molecular pathways that are MARCH-regulated.

Team members: Cyrus Tan and Raphael Trenker