(left to right) Emir Maldsosevi, Kinga Malezyna, Sara Zdancewicz, and Ahmad Jomaa, PhD, stand with the Titan Krios electron microscope, a powerful instrument used to capture the ribosome structures described in this study.
A new paper from the Jomaa Lab in the Department of Molecular Physiology and Biological Physics at UVA School of Medicine reveals how cells attach a lipid tag to certain proteins as they are made on ribosomes. The work, recently published in the EMBO Journal, uncovers the molecular mechanism by which the nascent polypeptide-associated complex (NAC) recruits the enzyme (N-myristoyltransferase 2) NMT2 to modify emerging proteins as they are being made on the ribosome.
Graduate student Sara Zdancewicz, lead author of the study, and colleagues used cryo-electron microscopy to show how NAC positions NMT2 on the ribosome to form a channel that guides nascent proteins to the enzyme’s catalytic site. This lipidation, called N-glycine myristoylation, enables proteins to reversibly associate with membranes, where they regulate essential processes such as signaling and stress responses. The study provides one the first detailed frameworks for how protein synthesis and lipid tagging are connected.
Although focused on fundamental mechanisms of protein biogenesis, the study may also help inform cardiovascular research. Independent studies have shown that NMT2 levels are lower in patients with cardiac hypertrophy and that disrupted lipidation of proteins such as MARCKS contributes to disease. By revealing how NAC and NMT2 work together on the ribosome, the UVA team lays groundwork for exploring how changes in this process could affect heart health.
The research team also includes biophysics graduate students from the Jomaa lab Emir Maldosevic and Kinga Malezyna, whose contributions alongside Zdancewicz provided key mechanistic insights into pathways that may underlie the onset of human disease.
Ahmad Jomaa, PhD, is an assistant professor in the Department of Molecular Physiology and Biological Physics.
Filed Under: Research