Available online at www.sciencedirect.com
Macromolecular assemblages
Editorial overview
Felix A Rey and Wesley I Sundquist
Current Opinion in Structural Biology 2011,
21:221–222
0959-440X/$ – see front matter
# 2011 Elsevier Ltd. All rights reserved.
DOI 10.1016/j.sbi.2011.03.001
Felix A Rey
Institut Pasteur, Department of Virology
Structural Virology Unit and CNRS URA3015,
25 rue du Dr Roux, 75015 Paris, France
e-mail: rey@pasteur.fr
Felix A. Rey is head of the Virology
Department at Institute Pasteur in Paris,
France. He also directs the Structural
Virology Unit of the Institute. Felix’s
research has focused on the study of
viruses using X-ray crystallography and
collaborating with electron microscopists
to dock atomic structures into cryo-EM
reconstructions in order to understand
the architecture of enveloped viruses. His
main focus has been on understanding
the membrane fusion process that takes
place during the entry of enveloped
viruses into a cell. He has also studied
the structure of nonenveloped virus
particles as well as viral polymerases and
viral ribonucleoprotein complexes.
Wesley I Sundquist
Department of Biochemistry, University of
Utah, School of Medicine, Salt Lake City,
UT 84103
e-mail: wes@biochem.utah.edu
Wes Sundquist is the Benning
Presidential Chair and Co-Chair of the
Department of Biochemistry at the
University of Utah in Salt Lake City, Utah.
Wes research interests center on the
structural, molecular and cell biology of
the human immunodeficiency virus.
Current efforts are aimed at defining the
mechanisms of HIV assembly and
budding, determining the structural
organization of mature and immature viral
particles, and elucidating the pathways
of viral capsid disassembly and cellular
restriction. His laboratory also studies the
role of the ESCRT pathway in cell
division.
As important as individual proteins and enzymes can be, most of the
important biological transformations within cells are carried out by multi-
component assemblies. Understanding cell biology therefore requires deter-
mining their structures and unraveling their mechanisms of action. The first
high-resolution pictures of complex macromolecular assemblies were pro-
vided by X-ray crystal structures of intact virus particles, some 30 years ago
[1,2]. That seminal work was followed by a series of landmark studies that
revealed the first structures of trans-membrane protein complexes [3],
structures of large cellular machines such as the proteasome [4] and the
GroEL chaperone [5], and the protein–nucleic acid complexes that define
the central dogma of molecular biology, including the nucleosome [6], DNA
[7,8] and RNA polymerases [9,10], prokaryotic ribosomes [11–14], and most
recently, the eukaryotic ribosome [15,16].
X-ray crystallography continues to be the dominant approach for defining
high-resolution structures of macromolecular complexes, and current fron-
tiers include defining the architectures of large supramacromolecular assem-
blies and obtaining multiple ‘snapshots’ of cellular machines that not only
reveal their molecular structures, but also help define precisely how they
function and are regulated. These principles are illustrated by a series of
outstanding reviews in this issue that describe the complex architectures of
capsid-like bacterial metabolic organelles, the structures and functions of
chaperones that help b-helical proteins to fold, the molecular gymnastics of
AAA ATPases and retroviral integrases, and the multi-faceted regulation of
the cullin-RING ubiquitin ligases. In each case, mechanistic insights were
greatly extended by generating multiple structures that revealed different
conformational states, captured key reaction intermediates, supported com-
parative analyses, and stimulated complementary biochemical analyses.
Indeed, it is now abundantly clear that no single structure can capture
the delightful complexity of important biological machines, and the differ-
ent reviews serve to remind us that an initial structure typically signifies the
beginning, not the end, of a modern structural analysis.
The past decade has also brought enormous progress in electron cryo-
microscopy methodologies, to the point where symmetric virus particles
(and similar favorable assemblies) can now be reconstructed at sufficiently
high-resolution to visualize and trace the polypeptide backbone. This
important development is reviewed by Grigorieff and Harrison in another
article in this issue. Cryo-EM approaches are also being used to produce
reconstructions of asymmetric single particles at slightly lower resolutions
that can nevertheless provide very important mechanistic insights, particu-
larly when combined with high-resolution crystallographic methods. Studies
of the ribosome have been among the most important in this regard, as
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