Every cell in our body interacts with its environment. These ever-lasting cellular conversations serve to pass crucial information important for promoting and maintaining numerous processes, which enable the cells to respond to their changing surroundings. Our lab utilizes cutting-edge methods in order to delineate the structural mechanisms underlying the activity and allosteric regulation of two types of enzymes: Ion channels, catalyzing the movement of ions across cell membranes, and prenyltransferases, synthesizing moieties for post-translational protein modification. Importantly, we focus on deciphering their essential roles for cellular proliferation and analyze pathophysiological mechanisms associated with cancerous transformation.
Welcome to the Haitin lab!
Structural Perspective of Ion Channels and Prenyltransferases Modulation
Ion channels are the key molecular elements, deeply involved in this cellular talk. These fascinating proteins facilitate the controlled passage of charged particles, the ions, through lipid membranes, which are otherwise impermeable hydrophobic barriers. Indeed, due to their critical biological roles, approximately 15% of all drugs target ion channels as their therapeutic receptors. Moreover, as all proteins, the structural organization of ion channels is tightly related to their diverse functions. Thus, it stands to reason that studying the molecular properties of these pivotal proteins is of extreme importance.
In principle, ion channels are best known for their activity in the brain and muscles. This makes a lot of sense in light of the fact that ion channels drive most of our cells’ electrical potential. For example, it would be impossible to lift a finger, or even to consider it, without the activity of voltage-gated sodium channels found in our muscles and neurons. However, it turns out that moving things and thinking thoughts are not the only things ion channels are good for. These amazing proteins are also abundant in non-excitable tissues, collectively known as “electrically boring” But, these tissues are anything but boring – some of the most interesting cells we know belong to this group, which includes the immune system and cancer cells to name a few.
Post-translational modifications (PTM) of proteins are crucial for their proper folding, cellular localization and thus, their biological function. Moreover, PTM add another layer of complexity, increasing the functional and structural diversity of the proteome. We study two members of the prenyltransferase enzyme superfamily, which play pivotal roles in PTM biogenesis and are involved in various devastating conditions, such as inherited blindness, epilepsy, neurodegeneration, and cancer. By studying their structure and function at the molecular level, we aim to decipher the mechanisms underlying their activities in health and disease.