TCELLTIGIT · Structural characterization of immune signaling protein TIGIT using x-ray crystallography and cryo-electron microscopy

Structural characterization of immune signaling protein TIGIT using x-ray crystallography and cryo-electron microscopy

Immunosignaling proteins are the target of anti-cancer and anti-viral immunotherapies. These proteins are known as single pass transmembrane receptors and consist of 3 parts: an extracellular domain (ECD), a transmembrane (TM) domain, and an intracellular domain (ICD). The TM domain is important because it allows signals to be transferred from the outside of the cell to the inside through the cell membrane. However, very little is known about the TM domains of these proteins because no structures have been solved that include this domain. The objective of this project was to solve a structure of the immunosignaling protein TIGIT (T cell immunoreceptor with Ig and ITIM domains) that contains the TM domain. The goal of this was to allow us to better understand how these immunosignaling proteins conduct signals through the cell membrane. Understanding the mechanism for how these protein conduct signals through the membrane bilayer is important because it could potentially result in the design of new anti-cancer and anti-viral immunotherapies targeting the TM domains of these proteins. However, the action was terminated early due to medical issues experienced by the fellow, so we note that not all of the objectives of the action could be accomplished given the circumstances.

Data: CORDIS, © European Union