Latest news with #BinLiu
Yahoo
3 days ago
- General
- Yahoo
New high-resolution structures of measles virus enzyme could lead to protective measures
May 30—Using high-resolution cryo-electron microscopy (cryoEM), researchers at The Hormel Institute, University of Minnesota, have revealed the first high-resolution renderings of the measles virus's (MeV) polymerase. This enzyme is crucial for the virus's ability to hijack cells and make copies of itself, which is one aspect that makes the virus so effective at infecting people and spreading throughout the body. For a virus that's been documented since at least the ninth century, there is still plenty we have to learn about the measles virus and how it operates, Associate Professor Bin Liu, PhD, explained as he discussed his new study published in Nature Communications. "Even well-known viruses like measles still have uncharted molecular terrain, and illuminating its structure provides valuable insights for therapeutic development," Liu said. By revealing measles' structure, Liu, along with Postdoctoral Researchers Dong Wang, PhD, and Ge Yang, PhD, have unlocked valuable insights that could help other researchers develop preventative and therapeutic measures to combat this deadly virus that can cause complications ranging from pneumonia to ear infections to encephalitis (inflammation of the brain). "Although an effective vaccine is available, recent measles outbreaks highlight the urgent need for alternative antiviral treatments," Liu said. "Because the polymerase is essential for viral genome replication, it represents a critical target for antiviral intervention." The study presents two new, distinct renderings of MeV polymerase complexes known as Lcore-P and Lfull-P-C. According to Liu, one of the most intriguing findings is the structural role of the measles virus C protein in forming the Lfull-P-C complex with two other proteins, L and P. This is surprising because the C protein was traditionally seen as a regulatory protein, not part of its core replication machinery. Now, it's shown to physically bridge and modulate the L protein's activity, potentially influencing how efficiently the virus replicates. Additionally, the study shows that the C protein widens the polymerase's RNA channel in the polymerase, possibly enhancing the processivity of RNA synthesis. That kind of physical alteration, revealed via cryoEM at near-atomic resolution, is a remarkable mechanistic insight. It suggests that the measles virus has evolved an elegant, multi-protein solution for efficient replication inside host cells. This kind of structural adaptation is a biological engineering marvel, and it highlights how even simple viruses can have complex, dynamic protein machinery. By revealing detailed interactions within the Lfull-P-C complex, the paper opens doors for next-generation antiviral drug designs that halt viral replication. "This shifts the measles conversation from 'solved by vaccines' to 'still relevant for therapeutic innovation,'" Liu concluded.
Yahoo
22-02-2025
- Health
- Yahoo
Nature study co-led by Institute professor sheds new light on process blood clotting, immune response
Feb. 21—Bin Liu, PhD, associate professor at The Hormel Institute, University of Minnesota, is among the authors of a newly published paper appearing in the leading scientific journal Nature, entitled "Molecular basis of vitamin K driven γ-carboxylation at membrane interface." The study, co-led by Dr. Weikai Li, PhD (Washington University, St. Louis, Missouri) and Dr. Liu, sheds new light on mechanisms involved with a process called γ-carboxylation and has implications for better understanding and treating hemostatic and non-hemostatic disorders. When you scrape your knee on the sidewalk, your body has to react quickly to stop the bleeding and protect you from infection. This complex response involves multi-step processes, starting with the formation of a blood clot, a process known as hemostasis. Hemostasis alone is a complex process that involves a number of highly orchestrated steps at the cellular level. One of the steps in hemostasis is known as γ-carboxylation (gamma carboxylation) — and the findings from this study offer new observations related to the process. Certain coagulation and anticoagulation proteins — proteins that aid or prevent blood clotting — have structural features rich in the amino acid glutamate. The enzyme vitamin K-dependent γ-carboxylase (VKGC) modifies these glutamates into γ-carboxyglutamyl (Gla) residues. From there, assisted by calcium ions, protein complexes are assembled that are crucial in carrying out a series of biochemical reactions allowing processes like hemostasis to take place. But hemostasis is only one crucial bodily process tied to γ-carboxylation. It is also significant for functions, such as inhibiting thrombosis (when blood clots block blood flow in vessels), calcium homeostasis (maintaining stable levels of calcium ions), immune response, and endocrine regulation. When γ-carboxylation isn't carried out properly, serious health problems can occur. Mutations in hemostatic proteins can interfere with γ-carboxylation and can cause hemophilia B, thrombophilia, and other bleeding complications. Deficient γ-carboxylation of certain proteins can lead to bone disorders and vascular calcification, which is connected to atherosclerosis and chronic kidney diseases. This makes the mechanisms surrounding γ-carboxylation a possible target for treating or preventing a vast array of related conditions. "We believe our findings will be of interest to a very broad audience, including scientists studying integral membrane enzymes, membrane biologists and structural biologists, cardiovascular biologists, hematologists, and pharmacologists, as well as clinical researchers and physicians," Liu. With the goal of better understanding the unique biochemistry, and using The Hormel Institute's cryogenic-sample electron microscopy (cryoEM) facilities, the team of researchers mapped seven cryoEM structures for analysis. These included VKGC in its unbound form, as well as in complex with the Prop-Glu of proteins that included factor IX (FIX), factor (FX), protein C, and transmembrane Gla protein 2 (TMG2) — each in different carboxylation states, as well as with and without KH2 . Representing a significant breakthrough for the field of membrane enzymology, these structures and supporting functional analyses reveal the mechanisms underlying multiple substrate specificity, coupling of epoxidation with carboxylation, and allosteric motions during VKGC catalysis.
