The transmembrane domain in viral fusion: Essential role for a conserved glycine residue in vesicular stomatitis virus G protein

Cleverley, Diane Z.; Lenard, John

doi:10.1073/pnas.95.7.3425

Cited by 139 publications

(171 citation statements)

References 63 publications

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“…The generality of these findings to other fusion proteins was suggested (Cleverley and Lenard, 1998). The HA of the A/Japan/305/57 strain used in the present study has two glycines within its TM domain; the one at position 530 is conserved among strains of influenza, whereas the glycine at position 520 (Figure 1) is a serine in most other strains.…”

Section: A Point Mutation In the Tm Domain Of Ha Inhibits Fusionsupporting

confidence: 72%

“…It had been shown that mutation of either one of the two glycines within the TM domain of the G protein of VSV attenuates the extent of fusion, whereas mutation of both glycines inhibits full fusion but supports hemifusion (Cleverley and Lenard, 1998). The generality of these findings to other fusion proteins was suggested (Cleverley and Lenard, 1998).…”

Section: A Point Mutation In the Tm Domain Of Ha Inhibits Fusionmentioning

confidence: 99%

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Amino Acid Sequence Requirements of the Transmembrane and Cytoplasmic Domains of Influenza Virus Hemagglutinin for Viable Membrane Fusion

Melikyan

Lin

Roth

et al. 1999

MBoC

121

135

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The amino acid sequence requirements of the transmembrane (TM) domain and cytoplasmic tail (CT) of the hemagglutinin (HA) of influenza virus in membrane fusion have been investigated. Fusion properties of wild-type HA were compared with those of chimeras consisting of the ectodomain of HA and the TM domain and/or CT of polyimmunoglobulin receptor, a nonviral integral membrane protein. The presence of a CT was not required for fusion. But when a TM domain and CT were present, fusion activity was greater when they were derived from the same protein than derived from different proteins. In fact, the chimera with a TM domain of HA and truncated CT of polyimmunoglobulin receptor did not support full fusion, indicating that the two regions are not functionally independent. Despite the fact that there is wide latitude in the sequence of the TM domain that supports fusion, a point mutation of a semiconserved residue within the TM domain of HA inhibited fusion. The ability of a foreign TM domain to support fusion contradicts the hypothesis that a pore is composed solely of fusion proteins and supports the theory that the TM domain creates fusion pores after a stage of hemifusion has been achieved. INTRODUCTIONMembrane fusion is common to many cellular processes, such as exocytosis and intracellular trafficking. But only in the case of viruses have the proteins responsible for fusion been unambiguously identified. A number of common features have been found among viral fusion proteins. All are oligomerized. The monomer of each oligomer always contains a critical stretch of nonpolar amino acids, known as the fusion peptide (Hernandez et al., 1996;Durell et al., 1997). As crystallographically determined, fusion proteins from several different virus families have the same backbone structure of extended coiled-coil ␣-helices (Bullough et al., 1994;Chan et al., 1997). Because viral fusion proteins of unrelated viruses have common structural patterns, it is logical to assume that their mechanisms of fusion are similar as well. Furthermore, a complex of SNARES, proteins thought to be responsible for the constitutive fusion of intracellular trafficking and the regulated fusion that occurs in exocytosis (Sü dhof, 1995), has been crystallographically determined (Poirier et al., 1998;Sutton et al., 1998). It too displays a long coiled-coil region. Therefore it may well be that the mechanisms of viral fusion pertain more generally to cellular fusion. Influenza virus has long been the prototypic virus for study of fusion mechanisms. It ‡ Corresponding author. E-mail address: fcohen@rush.edu. Abbreviations used: CF, carboxyfluorescein; CPZ, chlorpromazine; CT, cytoplasmic tail; DMEM, Dulbecco's modified Eagle's medium; GPI, glycosylphosphatidylinositol; HA, hemagglutinin; PBS-A-S, PBS supplemented with 0.1% sodium azide and 5% calf serum; p.i., postinfection; pIgR, polyimmunoglobulin receptor; R18, octadecylrhodamine B; RBC, red blood cell; RD, tetramethylrhodamine-tagged dextran; TM, transmembrane; VSV, vesicular stomatitis virus; WT,...

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Section: A Point Mutation In the Tm Domain Of Ha Inhibits Fusionsupporting

confidence: 72%

Section: A Point Mutation In the Tm Domain Of Ha Inhibits Fusionmentioning

confidence: 99%

Amino Acid Sequence Requirements of the Transmembrane and Cytoplasmic Domains of Influenza Virus Hemagglutinin for Viable Membrane Fusion

Melikyan

Lin

Roth

et al. 1999

MBoC

121

135

View full text Add to dashboard Cite

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“…First, the transmembrane domain is absent in the structures. However, it is known that it plays an important role at the late stages of the fusion process as mutations of transmembrane glycin residues block fusion at a hemifusion stage [78]. Second, the structures of intermediate conformations of G, how they cooperate and how they interact with and deform the viral and target membranes are still very elusive.…”

Section: Discussionmentioning

confidence: 99%

Structures of vesicular stomatitis virus glycoprotein: membrane fusion revisited

Roche

Albertini

Lepault

et al. 2008

Cell. Mol. Life Sci.

127

138

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Abstract. Glycoprotein G of the vesicular stomatitis virus (VSV) is involved in receptor recognition at the host cell surface and then, after endocytosis of the virion, triggers membrane fusion via a low pHinduced structural rearrangement. G is an atypical fusion protein, as there is a pH-dependent equilibrium between its pre-and post-fusion conformations. The atomic structures of these two conformations reveal that it is homologous to glycoprotein gB of herpesviruses and that it combines features of the previously characterized class I and class II fusion proteins.Comparison of the structures of G pre-and postfusion states shows a dramatic reorganization of the molecule that is reminiscent of that of paramyxovirus fusion protein F. It also allows identification of conserved key residues that constitute pH-sensitive molecular switches. Besides the similarities with other viral fusion machineries, the fusion properties and structures of G also reveal some striking particularities that invite us to reconsider a few dogmas concerning fusion proteins.

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“…In addition, it has also been shown that not only the ectodomain segment but also the membrane anchoring domain is required for VSV fusion activity (52,53).…”

Section: Determination Of the Rhabdovirus Fusion Peptidementioning

confidence: 99%

Viral membrane fusion: is glycoprotein G of rhabdoviruses a representative of a new class of viral fusion proteins?

Poian

Carneiro

Stauffer

2005

Braz J Med Biol Res

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Enveloped viruses always gain entry into the cytoplasm by fusion of their lipid envelope with a cell membrane. Some enveloped viruses fuse directly with the host cell plasma membrane after virus binding to the cell receptor. Other enveloped viruses enter the cells by the endocytic pathway, and fusion depends on the acidification of the endosomal compartment. In both cases, virus-induced membrane fusion is triggered by conformational changes in viral envelope glycoproteins. Two different classes of viral fusion proteins have been described on the basis of their molecular architecture. Several structural data permitted the elucidation of the mechanisms of membrane fusion mediated by class I and class II fusion proteins. In this article, we review a number of results obtained by our laboratory and by others that suggest that the mechanisms involved in rhabdovirus fusion are different from those used by the two well-studied classes of viral glycoproteins. We focus our discussion on the electrostatic nature of virus binding and interaction with membranes, especially through phosphatidylserine, and on the reversibility of the conformational changes of the rhabdovirus glycoprotein involved in fusion. Taken together, these data suggest the existence of a third class of fusion proteins and support the idea that new insights should emerge from studies of membrane fusion mediated by the G protein of rhabdoviruses. In particular, the elucidation of the three-dimensional structure of the G protein or even of the fusion peptide at different pH's might provide valuable information for understanding the fusion mechanism of this new class of fusion proteins. Correspondence

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The transmembrane domain in viral fusion: Essential role for a conserved glycine residue in vesicular stomatitis virus G protein

Cited by 139 publications

References 63 publications

Amino Acid Sequence Requirements of the Transmembrane and Cytoplasmic Domains of Influenza Virus Hemagglutinin for Viable Membrane Fusion

Amino Acid Sequence Requirements of the Transmembrane and Cytoplasmic Domains of Influenza Virus Hemagglutinin for Viable Membrane Fusion

Structures of vesicular stomatitis virus glycoprotein: membrane fusion revisited

Viral membrane fusion: is glycoprotein G of rhabdoviruses a representative of a new class of viral fusion proteins?

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