Viruses are small intracellular parasites that invade the cells of virtually all known organisms. They reproduce by utilizing the cell's machinery to replicate viral proteins and genomic material, generally damaging or killing the host cell in the process; subsequentelly, a large number of newly generated viruses go on to infect other cells. Viruses are responsible for a wide variety of human diseases, ranging from the common (influenza and colds) to the exotic (AIDS, West Nile virus and Zika). Some viruses which are not dangerous to humans can also be exploited in technological applications, in addition, viruses find use in genetic engineering applications and increasingly in the design of new nanomaterials. At the very least, all viruses contain two components: the capsid (a protein shell), and a genome, consisting of either DNA or RNA. Some viruses also include accessory proteins to aid in infection, and in some cases a lipid bilayer to further protect their contents from the environment. The viral life cycle itself is deceivingly simple: viruses enter the cell, typically (but not always) through the interaction of their capsid with a receptor on the cell surface; the virus must then somehow disassemble its capsid to release its genetic material and any necessary helper proteins. The viral genome is then replicated and the proteins it codes for are synthesized to produce the raw material for the production of new viral particles; these new viruses then assemble and bud from the cell either through the membrane or upon cell death.

Spotlight: Lung Surfactant Duality (Aug 2016)

SPA graphical abstract

image size: 1.7MB
made with VMD

Our lungs are coated with a layer of protein and lipid mixture called lung surfactant, which prevents the lungs from collapsing and protects us from bacterial and viral infections (see October 2012 and January 2014 highlights). Lung surfactant protein A (SP-A) - the major protein constituent of lung surfactant - plays a dual role. It aggregates DPPC lipid, a major component of lung membrane, into a lattice-like structure that prevents the lungs from collapsing. SP-A is also known to recognize and bind bacterial lipids, namely lipid A, on surfaces of gram-negative bacteria, thereby helping to initiate various clearance mechanisms. However, it was unclear how SP-A exhibits such functional duality with its binding to two different types of lipids. A recent study used molecular dynamics simulations with NAMD to unravel the dual role of SP-A. Combined with crystallographic and mutational analyses, researchers have discovered several critical, non-canonical lipid binding sites that involves cation-π interactions and hydrogen bonds. Simulations have also revealed that SP-A binds stronger to bacterial lipid (lipid A) than to surfactant lipid (DPPC lipid), which suggests SP-A may prioritize its host defense functions by transferring from lung membrane to bacterial surface. These findings in atomistic detail will enable experimentalists to enhance the antimicrobial function of SP-A. More on our lung surfactant protein website.

Related Spotlights

Related Publications
Related Research
Investigators
Publications Database
  • Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Gongpu Zhao, Juan R. Perilla, Ernest L. Yufenyuy, Xin Meng, Bo Chen, Jiying Ning, Jinwoo Ahn, Angela M. Gronenborn, Klaus Schulten, Christopher Aiken, and Peijun Zhang. Nature, 497:643-646, 2013.
  • Cyclophilin A stabilizes HIV-1 capsid through a novel non-canonical binding site. Chuang Liu, Juan R. Perilla, Jiying Ning, Manman Lu, Guangjin Hou, Ruben Ramalho, Gregory Bedwell, In-Ja Byeon, Jinwoo Ahn, Jiong Shi, Angela Gronenborn, Peter Prevelige, Itay Rousso, Christopher Aiken, Tatyana Polenova, Klaus Schulten, and Peijun Zhang. Nature Communications, 7:10714:(10 pages), 2016.
  • Dynamic allostery governs cyclophylin A-HIV capsid interplay. Manman Lu, Guangjin Hou, Huilan Zhang, Christopher L. Suiter, Jinwoo Ahn, In-Ja L. Byeon, Juan R. Perilla, Christopher J. Langmead, Ivan Hung, Peter L. Gor'kov, Zhehong Gan, William Brey, Christopher Aiken, Peijun Zhang, Klaus Schulten, Angela M. Gronenborn, and Tatyana Polenova. Proceedings of the National Academy of Sciences, USA, 112:14617-14622, 2015.
  • Atomic modeling of an immature retroviral lattice using molecular dynamics and mutagenesis. Boon Chong Goh, Juan R. Perilla, Matthew R. England, Katrina J. Heyrana, Rebecca C. Craven, and Klaus Schulten. Structure, 23:1414-1425, 2015.
  • HIV-1 capsid function is regulated by dynamics: Quantitative atomic-resolution insights by integrating magic-angle-spinning NMR, QM/MM, and MD. Huilan Zhang, Guangjin Hou, Manman Lu, Jinwoo Ahn, In-Ja L. Byeon, Christopher J. Langmead, Juan R. Perilla, Ivan Hung, Peter L. Gor'kov, Zhehong Gan, William W. Brey, David A. Case, Klaus Schulten, Angela M. Gronenborn, and Tatyana Polenova. Journal of the American Chemical Society, 138:14066-14075, 2016.
  • All-atom molecular dynamics of virus capsids as drug targets. Juan R. Perilla, Jodi A. Hadden, Boon Chong Goh, Christopher G. Mayne, and Klaus Schulten. Journal of Physical Chemistry Letters, 7:1836-1844, 2016.
  • Molecular dynamics simulations of the complete satellite tobacco mosaic virus. Peter L. Freddolino, Anton S. Arkhipov, Steven B. Larson, Alexander McPherson, and Klaus Schulten. Structure, 14:437-449, 2006.
  • Stability and dynamics of virus capsids described by coarse-grained modeling. Anton Arkhipov, Peter L. Freddolino, and Klaus Schulten. Structure, 14:1767-1777, 2006.
  • Funded by a grant from
    the National Institute of
    General Medical Sciences
    of the National Institutes
    of Health