Progress in structural biology very much depends upon the development
of new high-resolution techniques and tools. Despite decades of study of
viruses, bacteria and bacterial spores and their pressing importance in
human medicine and biodefense, many of their structural properties are
poorly understood. Thus, characterization and understanding of the
architecture of protein surface and internal structures of pathogens is
critical to elucidating mechanisms of disease, immune response,
physicochemical properties, environmental resistance and development of
countermeasures against bioterrorist agents. Furthermore, even though
complete genome sequences are available for various pathogens, the
structure-function relationships are not understood. Because of their
lack of symmetry and heterogeneity, large human pathogens are often
refractory to X-ray crystallographic analysis or reconstruction by
cryo-electron microscopy (cryo-EM). An alternative high-resolution
method to examine native structure of pathogens is atomic force
microscopy (AFM), which allows direct visualization of macromolecular
assemblies at near-molecular resolution. The capability to image single
pathogen surfaces at nanometer scale in vitro would profoundly impact
mechanistic and structural studies of Progress in structural biology
very much depends upon the development of new high-resolution techniques
and tools. Despite decades of study of viruses, bacteria and bacterial
spores and their pressing importance in human medicine and biodefense,
many of their structural properties are poorly understood. Thus,
characterization and understanding of the architecture of protein
surface and internal structures of pathogens is critical to elucidating
mechanisms of disease, immune response, physicochemical properties,
environmental resistance and development of countermeasures against
bioterrorist agents. Furthermore, even though complete genome sequences
are available for various pathogens, the structure-function
relationships are not understood. Because of their lack of symmetry and
heterogeneity, large human pathogens are often refractory to X-ray
crystallographic analysis or reconstruction by cryo-electron microscopy
(cryo-EM). An alternative high-resolution method to examine native
structure of pathogens is atomic force microscopy (AFM), which allows
direct visualization of macromolecular assemblies at near-molecular
resolution. The capability to image single pathogen surfaces at
nanometer scale in vitro would profoundly impact mechanistic and
structural studies of pathogenesis, immunobiology, specific cellular
processes, environmental dynamics and biotransformation.
Unraveling the Architecture and Structural Dynamics of Pathogens by
High-Resolution in vitro Atomic Force Microscopy