Structures of Abs bound to these stabilized proteins have allowed for the elucidation of neutralizing epitopes around the viral surface proteins

Structures of Abs bound to these stabilized proteins have allowed for the elucidation of neutralizing epitopes around the viral surface proteins. guided the design of new therapeutics and vaccines. An early pioneer in structural biology was the X-ray crystallographer Rosalind Franklin. While she is best known for her role in collecting the X-ray fiber diffraction patterns that revealed the 3D structure of DNA, her contributions in biologically-related fields also included insights into the structures of protein encapsulated viruses such as tobacco mosaic computer virus (TMV), poliovirus, and turnip yellow mosaic computer virus. During Franklins studies of viruses in the 1950s, a central question was how viruses managed to build a protein shell to shield their genetic material given that only a limited number of viral capsid proteins could be encoded within a viral genome based on capsid size constraints. Mouse monoclonal to Metadherin Franklins X-ray analysis revealed the arrangement of the protein subunits in TMV, allowing her to create the first three-dimensional model of a computer virus [1,2,3,4]. Following this work, she used X-ray data to determine the position and orientation of RNA packaged inside of the rod-shaped TMV [5]. Unlike prior speculation that placed the RNA at the center of the rod, her work revealed the computer virus was hollow, which led to the discovery that this RNA spiraled with the helical protein capsid. This work was fundamental in understanding principles of computer virus structure. Franklins contributions to the field RC-3095 of virology are summarized on her tombstone, which reads, Her research and discoveries on viruses remain of lasting benefit to mankind. Together, her amazing contributions to structural studies in three individual areas, DNA, coal, and viruses, before her death at the age of 37 make her an inspiration to future generations of structural biologists, particularly women. We are proud to follow in her footsteps to use structural biology to gain insight into viruses with the goal of providing benefits to human health. The severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic of 2002, Middle East Respiratory Syndrome (MERS) epidemic of 2012, acquired immune deficiency syndrome (AIDS) pandemic starting in 1981, the Zika computer virus (ZIKV) epidemic of 2015-2016, and the ongoing SARS-CoV-2/COVID-19 pandemic are examples of the enormous global burden of viruses and the urgent need for vaccine and therapeutic development. Building on the prior contributions of early pioneers such as Rosalind Franklin, structural biologists continue to advance techniques in X-ray crystallography and cryo-electron microscopy (cryo-EM) to investigate viruses and viral proteins. We are interested in investigating antibody (Ab) recognition of viruses, which we do by solving 3D structures of viral proteins bound to Abs elicited by contamination or vaccination. Understanding the structural correlates of Ab recognition of viruses is usually RC-3095 key for the development of effective monoclonal Ab therapies and vaccines (Physique 1). Open in a separate window Physique 1 Schematic of Ab characterization and therapeutic development. The binding epitopes of Abs isolated from infected or vaccinated individuals or animal studies are decided through structural analysis of Fabviral antigen complexes. These structures inform the design of vaccines, monoclonal Abs, and small molecule therapeutics that can be tested in clinical trials and animal models. Surface representations are shown for the following structures: FabSARS-CoV-2 S (PDB 7K90), FabZIKV EDIII (PDB 5VIG), FabHIV-1 Env (PDB 5T3Z), and small molecule inhibitorHIV-1 Env (PDB 7LO6). Human immunodeficiency computer virus 1 (HIV-1) is responsible for the AIDS pandemic and 36 million deaths to date [6] and has long posed a challenge for vaccine development due its amazing ability to evade the host immune response and establish latent reservoirs. HIV-1 contains a single viral protein on its surface that facilitates contamination of immune cells. This protein, named Envelope or Env, is usually a trimer of gp120/gp41 heterodimers (Physique 2A). The gp120 portion of Env interacts with host CD4 receptors, which stimulates conformational changes that allow binding RC-3095 to the co-receptor, usually a host chemokine receptor called CCR5 [7]. These events trigger rearrangements in gp41 that allow fusion of the viral and host cell membranes, which is required for entry RC-3095 of the HIV-1 genome into the host cell [7]. In addition to small molecule anti-retroviral drug treatments to treat infected individuals, current strategies to prevent HIV-1 contamination include vaccine design. Vaccine efforts seek to stimulate the evolution of broadly neutralizing Abs (bNAbs) that have been isolated in rare cases of human HIV-1 infection and are capable of broad and potent protection [8,9,10]. Advances in X-ray.