Structures of virus and virus-like particles

doi:10.1016/S0959-440X(00)00073-7

Current Opinion in Structural Biology

Volume 10, Issue 2, 1 April 2000, Pages 229-235

https://doi.org/10.1016/S0959-440X(00)00073-7 Get rights and content

Abstract

Virus structures continue to be the basis for mechanistic virology and serve as a paradigm for solutions to problems concerning macromolecular assembly and function in general. The use of X-ray crystallography, electron cryomicroscopy and computational and biochemical methods has provided not only details of the structural folds of individual viral components, but also insights into the structural basis of assembly, nucleic acid packaging, particle dynamics and interactions with cellular molecules.

Introduction

Structural virology has made remarkable progress in a variety of areas during the past two years. Recent reviews have dealt with specialized topics associated with virus structure and assembly 1, 2. Here, we will review topics that directly relate to virus and virus-like particles, and their interactions with cellular proteins. We include results obtained with methods used to directly visualize particle structure, such as electron cryomicroscopy (cryo-EM) and X-ray crystallography 3, 4•, as well as biochemical methods. These biophysical and biochemical techniques have been enhanced through the use of recombinant expression and/or assembly systems that allow the formation of virus-like-particles that may contain a different number and combination of capsid proteins compared with native particles. A number of the recent studies illustrate the complimentary nature of cryo-EM and crystallography [5]. The use of low-resolution models from cryo-EM for the initial phasing of the X-ray diffraction intensities, followed by icosahedral symmetry averaging, has now become a common procedure for solving the crystal structures of virus and virus-like particles 6••, 7••, 8••.

The review is organized into three sections: new insights into the properties, assembly and maturation of virus particles; analyses of viral particles interacting with antibodies and receptors; and the outlook for the future of structural studies of viruses and how they relate to the larger picture of structural biology.

Section snippets

New folds and features of viral capsid subunits

The canonical virus β sandwich continues to be the most common folding motif in capsid subunits of newly solved structures. New folds have also been discovered in recently determined virus structures, however, either as an independent subunit or as a separate domain fused with a β sandwich.

Norwalk virus, a single-stranded (ss) RNA virus, is the cause of one of the most serious intestinal disorders in the USA. The organization of its subunit and particle, which were expressed and assembled from

Identification of the locations and functional roles of gene products and sequence domains

Identifying the locations and functions of particular gene products in a complex virus structure is an important goal of structural virology. It is now common to utilize the expression of proteins in the baculovirus vector. In optimal cases, it is possible to have separate genes expressed in different baculovirus constructs that infect the same insect cell [21]. These have resulted in the formation of particles with subunits as determined by the particular baculovirus vectors introduced. This

Complexes of viral particles with antibodies and receptors

Cryo-EM has been used to determine low-resolution structures (20–25 Å) of viral particles complexed with IgG, antibodies or receptors. The most useful information that has been derived from these studies is the location of the epitopes and the relative orientation of the attached molecules with respect to the viral capsid 39, 40, 41, 42•, 43, 44. The relative orientation of the attached cellular protein was shown to be critical to its activity. For instance, two antibodies that bind to the same

Future outlook

The recently determined high-resolution structures of capsid proteins have shown a number of new folds compared with the commonly known β sandwich. It is likely that the continuous effort in studying high-resolution structures of other viral capsids will add to the structural genomics database of new folds, as well as identify existing folds of nonviral proteins used as part of a large viral capsid protein. Furthermore, the challenge of visualizing detailed features of nonicosahedrally

Note added in proof

Recently, the VIrus Particle ExploreR (VIPER) web site was established (http://mmtsb.scripps.edu/viper.viper.html). It contains the coordinates, in a standard orientation, of all the icosahedral viruses submitted to the Protein Data Bank. Graphics illustrating the particle morphology, the subunit fold(s) and the quasi-symmetry of the virus are provided. The stabilization energies for all unique subunit interfaces are tabulated, as well as residue-wise contributions to these stabilities.

Acknowledgements

We acknowledge the support of grants from the National Institutes of Health (GM34220, GM54076, AI38469, AI43656 and RR02250) and the R Welch Foundation. We thank Wen Jiang and Vijay Reddy for assistance in preparing the figures.

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

• of special interest
•• of outstanding interest

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ReviewStructures of virus and virus-like particles

Abstract

Introduction

Section snippets

New folds and features of viral capsid subunits

Identification of the locations and functional roles of gene products and sequence domains

Complexes of viral particles with antibodies and receptors

Future outlook

Note added in proof

Acknowledgements

References and recommended reading

Curr Opin Struct Biol

Adv Virus Res

Mol Cell

Structure

Cell

Cell

Biophys J

Biophys J

Cell

J Biol Chem

Virology

J Mol Biol

Virology

Principles of virus structure determination

Reconstruction principles of icosahedral virus structure determination using electron cryomicroscopy

Micron

Complementing crystallography: the role of cryo-electron microscopy in structural biology

Acta Crystallogr D Biol Crystallogr

The atomic structure of the blue tongue virus core

Nature

X-ray crystallographic structure of the Norwalk virus capsid

Science

Determination of the fold of the core protein of hepatitis B virus by electron cryomicroscopy

Nature

Visualization of a 4-helix bundle in the hepatitis B virus capsid by cryo-electron microscopy

Nature

The crystal structure of bluetongue virus VP7

Nature

The crystal structure of cricket paralysis virus: the first view of a new virus family

Nat Struct Biol

Visualization of protein-RNA interactions in cytoplasmic polyhedrosis virus

J Virol

The structure of a cypovirus and the functional organization of dsRNA viruses

Nat Struct Biol

Visualization of tegument/capsid interactions and DNA in intact herpes simplex virus type 1 virions

J Virol

Review
Structures of virus and virus-like particles