By Maria Solano, Contributing Writer
On Thursday, biochemist and professor Anirban Banerjee presented his research, “How the Fat Gets on Proteins, Structure and Mechanism of Enzymes that Catalyze Protein Palmitoylation,” at the Science Center. The event ran from 11:30 a.m. to 1 p.m. and was sponsored by The Sceptical Chymists, the faculty Events Planning and Coordinating Committee (EPACC) and the Department of Chemistry and Biochemistry as part of a seminar series that brings speakers to campus.
Banerjee is the senior investigator at the section on Structural and Chemical Biology Neurosciences and Cellular and Structural Biology division at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of National Institutes of Health (NIH). Banerjee said his interest in membrane proteins developed from the limited understanding of the chemical processes within them; he mentioned “we are really at the infancy of even beginning to understand at the chemical level how all of that works, so that is why I became fascinated with membrane proteins.”
One of the major areas of interest in Banerjee’s lab is membrane enzymes that catalyze protein lipidation. His research focuses on enzymes called DHHC palmitoyltransferases, as well as iron transportation into mitochondria.
The main focus of the presentation was the structure and chemical biology of enzymes that catalyze particular protein modification. Banerjee described protein S-acylation, also known as protein palmitoylation as, “by far the most abundant form of protein lipidation that we know of.” Palmitoylation, Banerjee said, is “ a reversible way of attaching a hydrophobic stick onto a protein.” The modification regulates protein localization and function across membranes.
The talk began by explaining soluble proteins and membrane proteins. Banerjee discussed how there is still a very basic understanding of how lipids shape membrane structure and function.
Another major point of the lecture was DHHC palmitoyltransferases. Humans have 23 DHHC enzymes, Banerjee said, “These so-called DHHC enzymes catalyze this modification and are localized in different organellar membranes.”
Banerjee’s lab worked to characterize DHHC using X-ray crystallography to determine structure. Banerjee mentioned the challenges involved and the methodology. “These crystals are obtained from so-called lipidic cubic phase, it took I think many more years for us to get the crystals.”
By using X-ray crystallography to identify membrane-embedded active site, the researchers looked to better understand the process of palmitoylation. Banerjee shared his findings. “The active site is in the membrane, and that explained right away why membrane-proximal cysteines are palmitoylated.”
For future membrane targets, the lab will adopt cryogenic electron microscopy, otherwise referred to as cryo-EM. “Cryo-EM is more linear, but you still need the same analytical‑quality samples, cryo-EM does not make everything super easy,” Banerjee explained.
The presentation concluded with a brief time for attendees to ask questions about the research and possible next steps.
Banerjee discussed the next steps, and the team plans to use CRISPR gene editing to modify the native DHHC20 enzyme. “What we are going to do next is to genetically, using CRISPR‑Cas, alter the native DHHC20 to the analog‑compatible mutant, and then do this experiment at the native level of DHHC20, paired with honed proteomic techniques to pick up the finer changes.”
After the question and answer time, Banerjee talked about postgraduate opportunities and summer internships at the NIH. He explained the process to apply, potential benefits from participating and advice for students interested.
One biochemistry student described the seminar series as providing “good exposure and also a good way to see how the things I’ve learned in all my classes come together in different areas.”
