Structure of human metapneumovirus RNA polymerase complex
Junhua Pan
Research Associate at Harvard Medical School
Host: 段金桥教授
Date: July. 12, 2023 (Wednesday)
Time: 16:00-17:00 P.M.
Venue: Tencent Meeting ID:255-688-252
国际创新创业社区A5栋19楼01会议室
Abstract:
Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) (pneumoviridae) are non-segmented negative sense RNA viruses (nsNSVs) that cause severe respiratory diseases in infants and elderlies. Neither a vaccine nor an effective antiviral therapy is available for treating or preventing RSV and HMPV infections. We describe a cryo-EM reconstruction showing the ring-shaped structure of the polymerase and capping domains of the HMPV L protein, bound to a tetramer of the phosphoprotein (P) cofactor. The priming loop important for initiation of RNA synthesis is fully retracted, leaving space in the active-site cavity for RNA elongation. P interacts extensively with the N-terminal region of L, with its coiled-coil tetramerization domain and long C-terminal extensions projecting from it wrapping around L like tentacles. The structural versatility of the four P protomers, largely disordered in free state, demonstrates a “folding-upon-partner-binding” mechanism for carrying out P adaptor functions. We propose a model for P modulating the multiple functions of L. The structure should accelerate the design of specific antiviral drugs. Future perspectives on the regulation of transcription and replication and the role of structural dynamics on coordinating the multi-enzymatic activities of L will also be discussed.
Biography:
Junhua Pan is a Research Associate at Harvard Medical School. He earned his B.S. degree in Food Science & Engineering from Wuhan Polytechnic University, M.S. degree in Bioengineering from Jiangnan University, and Ph.D. degree in Biochemistry & Cell Biology from Rice University. He was an HHMI postdoctoral fellow with Stephen C. Harrison at Boston Children’s Hospital (BCH) & Harvard Medical School Department of Biological Chemistry & Molecular Pharmacology (BCMP). Dr. Pan is an extensively experienced structural biologist, biochemist and virologist. He uses these methods to study mechanisms of viral genome organization, replication and transcription, receptor binding, membrane fusion by viral surface proteins, and immune response to prominent viruses such as influenza virus, HIV-1 and SARS-CoV-2. He is also dedicated to engineering viral proteins and viruses into tools for basic research and clinical applications, including high-throughput structural determination, immunogen design and precision targeting medicine against infectious diseases and solid-state tumor. Dr. Pan’s work has been published by top journals, such as Nature, Science, Cell and PNAS, and his engineering work has been patented. His most recent work on herpes viruses, alphaviruses, and other nsNSVs are either under review by or under preparation for these journals. He has served as an organizer for scientific conferences and a peer reviewer for journals such as Nature Communications, Communications Biology, and Bioconjugate Chemistry. Dr. Pan is also passionate in promoting basic and medicinal research in his previous fields such as food sciences and microbial fermentation.