Biophysical Society Thematic Meeting

Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Speaker Abstracts

Cryo-EM of Helical Polymers

Edward Egelman

University of Virginia, Charlottesville, VA, USA.

Cryo-EM has undergone a revolution, driven by direct electron detectors, and a near-atomic level

of resolution can now be reached for many biological samples. While complexes such as the

ribosome can be solved at higher resolution and more readily by cryo-EM than they can be by

crystallography, they can still be crystallized. However, a vast number of complexes of

biological interest are helical polymers, and most of these can never be crystallized. I will

describe the application of cryo-EM to helical assemblies in four different areas: 1)

Vibrio

cholera

, the organism responsible for cholera, uses a Type Six Secretion System in pathogenesis.

We now understand in detail how parts of this system assemble and work. 2) Type IV pili are

essential for the infectivity of bugs such as

Neisseria meningitidis

. We have shown

for

Campylobacter jejuni

(responsible for most food-borne illnesses in the world) that the

conserved flagellin protein can be assembled into different quaternary structures by small amino

acid changes. We show the same thing for Type IV pilins. 3) Flexible filamentous plant viruses

are responsible for half of the viral agricultural crop damage, but have resisted all attempts at

structure determination since the studies of J.D. Bernal >75 years ago. We have solved the

structure of two members of this family, bamboo mosaic virus (BaMV) and wheat streak mosaic

virus (WSMV) and show how, because they are completely non-toxic, they can be used in

biotechnology, in everything from medical imaging to serving as platforms for vaccines. 4)

Viruses that infect hyperthermophilic archaea can survive in nearly boiling acid or organic

solvents. We now understand how the stability of DNA in SIRV2 and AFV1 is achieved. AFV1,

like Ebola, is a filamentous membrane-enveloped virus, and we present the first atomic structure

of such a virus.