Viral membrane fusion

Harrison, Stephen C.

doi:10.1038/nsmb.1456

ScienceOpen: research and publishing network

For Publishers

For Researchers

Blog
About

Search
Advanced search

128

views

recommends

Record: found
Abstract: found
Article: not found

Viral membrane fusion

research-article

Author(s): Stephen C Harrison

Publication date PMC-release: 1 January 2009

Journal: Nature structural & molecular biology

Read this article at

ScienceOpenPublisher PMC

Bookmark

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Infection by viruses having lipid-bilayer envelopes proceeds through fusion of the viral membrane with a membrane of the target cell. Viral ‘fusion proteins’ facilitate this process. They vary greatly in structure, but all seem to have a common mechanism of action, in which a ligand-triggered, large-scale conformational change in the fusion protein is coupled to apposition and merger of the two bilayers. We describe three examples—the influenza virus hemagglutinin, the flavivirus E protein and the vesicular stomatitis virus G protein—in some detail, to illustrate the ways in which different structures have evolved to implement this common mechanism. Fusion inhibitors can be effective antiviral agents.

Related collections

Most cited references 58

Record: found
Abstract: found
Article: not found

Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin.

J Skehel, D Wiley (2000)

Hemagglutinin (HA) is the receptor-binding and membrane fusion glycoprotein of influenza virus and the target for infectivity-neutralizing antibodies. The structures of three conformations of the ectodomain of the 1968 Hong Kong influenza virus HA have been determined by X-ray crystallography: the single-chain precursor, HA0; the metastable neutral-pH conformation found on virus, and the fusion pH-induced conformation. These structures provide a framework for designing and interpreting the results of experiments on the activity of HA in receptor binding, the generation of emerging and reemerging epidemics, and membrane fusion during viral entry. Structures of HA in complex with sialic acid receptor analogs, together with binding experiments, provide details of these low-affinity interactions in terms of the sialic acid substituents recognized and the HA residues involved in recognition. Neutralizing antibody-binding sites surround the receptor-binding pocket on the membrane-distal surface of HA, and the structures of the complexes between neutralizing monoclonal Fabs and HA indicate possible neutralization mechanisms. Cleavage of the biosynthetic precursor HA0 at a prominent loop in its structure primes HA for subsequent activation of membrane fusion at endosomal pH (Figure 1). Priming involves insertion of the fusion peptide into a charged pocket in the precursor; activation requires its extrusion towards the fusion target membrane, as the N terminus of a newly formed trimeric coiled coil, and repositioning of the C-terminal membrane anchor near the fusion peptide at the same end of a rod-shaped molecule. Comparison of this new HA conformation, which has been formed for membrane fusion, with the structures determined for other virus fusion glycoproteins suggests that these molecules are all in the fusion-activated conformation and that the juxtaposition of the membrane anchor and fusion peptide, a recurring feature, is involved in the fusion mechanism. Extension of these comparisons to the soluble N-ethyl-maleimide-sensitive factor attachment protein receptor (SNARE) protein complex of vesicle fusion allows a similar conclusion.

0 comments Cited 725 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Core structure of gp41 from the HIV envelope glycoprotein.

David Chan, Deborah Fass, James M Berger … (1997)

The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) consists of a complex of gp120 and gp41. gp120 determines viral tropism by binding to target-cell receptors, while gp41 mediates fusion between viral and cellular membranes. Previous studies identified an alpha-helical domain within gp41 composed of a trimer of two interacting peptides. The crystal structure of this complex, composed of the peptides N36 and C34, is a six-helical bundle. Three N36 helices form an interior, parallel coiled-coil trimer, while three C34 helices pack in an oblique, antiparallel manner into highly conserved, hydrophobic grooves on the surface of this trimer. This structure shows striking similarity to the low-pH-induced conformation of influenza hemagglutinin and likely represents the core of fusion-active gp41. Avenues for the design/discovery of small-molecule inhibitors of HIV infection are directly suggested by this structure.

0 comments Cited 343 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Structure of the dengue virus envelope protein after membrane fusion.

Yorgo Modis, Steven Ogata, David K. Clements … (2004)

Dengue virus enters a host cell when the viral envelope glycoprotein, E, binds to a receptor and responds by conformational rearrangement to the reduced pH of an endosome. The conformational change induces fusion of viral and host-cell membranes. A three-dimensional structure of the soluble E ectodomain (sE) in its trimeric, postfusion state reveals striking differences from the dimeric, prefusion form. The elongated trimer bears three 'fusion loops' at one end, to insert into the host-cell membrane. Their structure allows us to model directly how these fusion loops interact with a lipid bilayer. The protein folds back on itself, directing its carboxy terminus towards the fusion loops. We propose a fusion mechanism driven by essentially irreversible conformational changes in E and facilitated by fusion-loop insertion into the outer bilayer leaflet. Specific features of the folded-back structure suggest strategies for inhibiting flavivirus entry.

0 comments Cited 315 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Jack and Eileen Connors Structural Biology Laboratory, Harvard Medical School, Laboratory of Molecular Medicine, Children’s Hospital Boston, and Howard Hughes Medical Institute, 250 Longwood Avenue, Boston, Massachusetts 02115, USA

Journal

Journal ID (nlm-journal-id): 101186374

Journal ID (pubmed-jr-id): 31761

Journal ID (nlm-ta): Nat Struct Mol Biol

Title: Nature structural & molecular biology

ISSN (Print): 1545-9993

ISSN (Electronic): 1545-9985

Publication date Nihms-submitted: 23 July 2008

Publication date (Print): July 2008

Publication date PMC-release: 1 January 2009

Volume: 15

Issue: 7

Pages: 690-698

Affiliations

Author notes

Correspondence should be addressed to S.C.H. ( harrison@ 123456crystal.harvard.edu )

Article

Manuscript ID: nihpa58717

DOI: 10.1038/nsmb.1456

PMC ID: 2517140

PubMed ID: 18596815

SO-VID: c4d8c32d-b5cf-491a-9c32-032079904c4b