PDB Molecule of the Month

Broadly Neutralizing Antibodies
Viruses like HIV and influenza have evolved sneaky methods for evading our immune system. The immune system searches for foreign molecules, but several viruses have found ways to hide their unique parts and masquerade as normal human molecules. They do this in many ways. As viral surface glycoproteins are synthesized in infected cells, they are decorated with the same sugar chains that coat human proteins, providing an effective camouflage. The conserved functional sites of the viral protein are hidden deep in a pocket surrounded by these sugars, and thus are difficult for antibodies to reach. In addition, these viruses have error-prone replication machinery, which creates a great diversity in the viral glycoproteins. So unfortunately, once the immune system has found antibodies to recognize the infecting virus, other viruses rapidly mutate to change the site that is recognized. Read More

HIV Envelope Glycoprotein
Viruses are faced with a tricky problem: they need to get inside cells, but cells are surrounded by a protective membrane. Enveloped viruses like HIV and influenza, which are themselves surrounded by a similar membrane, solve this problem by fusing with the cell membrane. The envelope glycoprotein (Env) of HIV performs the many complex steps needed for membrane fusion. First, it attaches itself to proteins on the surface of the cell. Then, it acts like a spring-loaded mousetrap and snaps into a new conformation that drags the virus and cell close enough that the membranes fuse. Finally, the HIV genome is released into the cell, where it quickly gets to work building new viruses. Read More

T-Cell Receptor
Viruses are one of the major dangers that we face in everyday life, so our immune system has powerful methods to fight them. Our cells call for help when they become infected, by displaying little pieces of the viruses on their surface. When the immune system finds these viral peptides, it quickly kills the infected cell and the viruses inside. Last month, we saw how an infected cell displays viral peptides using MHC. This month, we will look at the T-cell receptor, the protein that recognizes these viral peptides. Read More

Antibodies
Antibodies are our molecular watchdogs, waiting and watching for viruses, bacteria and other unwelcome visitors. Antibodies circulate in the blood, scrutinizing every object that they touch. When they find an unfamiliar, foreign object, they bind tightly to its surface. In the case of viruses, like rhinovirus or poliovirus presented last month in the Molecule of the Month, a coating of bound antibodies may be enough to block infection. Antibodies alone, however, are no match for bacteria. When antibodies bind to a bacterial surface, they act as markers alerting the other powerful defensive mechanisms available in the immune system. Read More

Catalytic Antibodies
Researchers have used the incredible functional diversity of the immune system in a clever way: to design new enzymes. Enzymes work by easing molecules through a difficult chemical change. For instance, look at the Diels-Alder reaction shown here at the bottom of the illustration. The two molecules on the left come together, forming an unstable intermediate shown at the center in red. Then, the intermediate falls apart, releasing sulfur dioxide and forming the desired product, shown on the right. Enzymes act by stabilizing the intermediate, smoothing the path from start to finish. Read More

SARS-CoV-2 Spike
The research community has quickly mobilized to fight the current SARS-CoV-2 pandemic, building on years of work on the previous SARS-CoV virus. The spike protein of this virus will be a central figure in this fight, since it is the primary target of antibodies that provide immunity against the virus. The surfaces of coronaviruses are covered with these spikes, giving them their distinctive crown-like appearance in electron micrographs. The spikes initiate the process of infection, binding to receptors and then fusing with the cell membrane to release the viral genome inside. Many other enveloped viruses use similar spike-like proteins to infect cells, including influenza hemagglutinin, and the envelope glycoproteins of HIV-1 and ebola. Read More