Biology Reference
In-Depth Information
tegument protein VP22 is found exclusively in the cytoplasm of
infected cells.
31
Viral nucleoid synthesis and envelope production may
proceed independently under certain conditions, leading to over-
production and release of empty envelopes. While these particles
are non-infectious, whether or not they can still interfere with cell
function and/or autoimmunity remains to be studied.
Cryo-Electron Microscopy and Tomography as Tools
for Herpesvirus Structure Determination
Herpesviruses are particularly challenging to structural biologists
because of their large size, the structural complexity of their capsids, and
the pleomorphic nature of their virion envelope and tegument layers.
These unusual properties make the synergistic use of cryo-electron
microscopy and single-particle reconstruction (commonly referred to
collectively as “cryoEM”) and cryo-electron tomography (cryoET) par-
ticularly important for structural studies of herpesviruses. Below, we will
provide a general technical account of cryoEM and cryoET in herpesvirus
structural studies, as well as specific examples of herpesvirus structures.
Although X-ray crystallography is the method of choice for reveal-
ing the atomic structures of large macromolecules and viruses, recent
advances have given cryoEM an increasingly important role in deter-
mining subnanometer-resolution structures of such complexes.
32-36
Because the samples are frozen-hydrated rather than crystallized,
cryoEM can reveal additional information about an entire virus'
structure in its native form even when the crystal structures of viral
components are already available.
Previously, cryoEM had been used only as a low-resolution tech-
nique (15-30 Å) due to the inevitable high level of noise in low-dose
cryoEM images. In the last few years, however, much progress has
made to demonstrate the feasibility of using cryoEM to resolve three-
dimensional (3D) structures of icosahedral virus particles at sub-
nanometer (6-9 Å) resolution.
32-35,37
This development represents a
significant step forward, as
de novo
structure determination by
cryoEM can now reveal new structural features such as
α
-helices and
β
-sheets
34-36,38
and uncover novel protein folds (see review by Zhou
