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J Virol
1994 Mar 01;683:1551-63. doi: 10.1128/JVI.68.3.1551-1563.1994.
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Influenza A virus M2 ion channel protein: a structure-function analysis.
Holsinger LJ
,
Nichani D
,
Pinto LH
,
Lamb RA
.
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A structure-function analysis of the influenza A virus M2 ion channel protein was performed. The M2 protein of human influenza virus A/Udorn/72 and mutants containing changes on one face of the putative alpha helix of the M2 transmembrane (TM) domain, several of which lead to amantadine resistance when found in virus, were expressed in oocytes of Xenopus laevis. The membrane currents of oocytes expressing mutant M2 ion channels were measured at both normal and low pH, and the amantadine-resistant mutant containing the change of alanine at residue 30 to threonine was found to have a significantly attenuated low pH activation response. The specific activity of the channel current of the amantadine-resistant mutants was investigated by measuring the membrane current of individual oocytes followed by quantification of the amount of M2 protein expressed in these single oocytes by immunoblotting analysis. The data indicate that changing residues on this face of the putative alpha helix of the M2 TM domain alters properties of the M2 ion channel. Some of the M2 proteins containing changes in the TM domain were found to be modified by addition of an N-linked carbohydrate chain at an asparagine residue that is membrane proximal and which is not modified in the wild-type M2 protein. These N-linked carbohydrate chains were further modified by addition of polylactosaminoglycan. A glycosylated M2 mutant protein (M2 + V, A30T) exhibited an ion channel activity with a voltage-activated, time-dependent kinetic component. Prevention of carbohydrate addition did not affect the altered channel activity. The ability of the M2 protein to tolerate deletions in the TM domain was examined by expressing three mutants (del29-31, del28-31, and del27-31) containing deletions of three, four, and five residues in the TM domain. No ion channel activity was detected from expression of M2 del29-31 and del27-31, whereas expression of M2 del28-31 resulted in an ion channel activity that was activated by hyperpolarization (and not low pH) and was resistant to amantadine block. Examination of the oligomeric form of M2 del28-31 indicated that the oligomer is different from wild-type M2, and the data were consistent with M2 del28-31 forming a pentamer.
Anderson,
Polylactosaminoglycan modification of the respiratory syncytial virus small hydrophobic (SH) protein: a conserved feature among human and bovine respiratory syncytial viruses.
1992, Pubmed
Anderson,
Polylactosaminoglycan modification of the respiratory syncytial virus small hydrophobic (SH) protein: a conserved feature among human and bovine respiratory syncytial viruses.
1992,
Pubmed
Ciampor,
Regulation of pH by the M2 protein of influenza A viruses.
1992,
Pubmed
Ciampor,
Evidence that the amantadine-induced, M2-mediated conversion of influenza A virus hemagglutinin to the low pH conformation occurs in an acidic trans Golgi compartment.
1992,
Pubmed
Doms,
Folding and assembly of viral membrane proteins.
1993,
Pubmed
Duff,
The secondary structure of influenza A M2 transmembrane domain. A circular dichroism study.
1992,
Pubmed
Duff,
The transmembrane domain of influenza A M2 protein forms amantadine-sensitive proton channels in planar lipid bilayers.
1992,
Pubmed
Folander,
Cloning and expression of the delayed-rectifier IsK channel from neonatal rat heart and diethylstilbestrol-primed rat uterus.
1990,
Pubmed
,
Xenbase
Goldstein,
Site-specific mutations in a minimal voltage-dependent K+ channel alter ion selectivity and open-channel block.
1991,
Pubmed
,
Xenbase
Grambas,
Maturation of influenza A virus hemagglutinin--estimates of the pH encountered during transport and its regulation by the M2 protein.
1992,
Pubmed
Grambas,
Influence of amantadine resistance mutations on the pH regulatory function of the M2 protein of influenza A viruses.
1992,
Pubmed
Hay,
The molecular basis of the specific anti-influenza action of amantadine.
1985,
Pubmed
Heginbotham,
The aromatic binding site for tetraethylammonium ion on potassium channels.
1992,
Pubmed
Helenius,
Unpacking the incoming influenza virus.
1992,
Pubmed
Holsinger,
Influenza virus M2 integral membrane protein is a homotetramer stabilized by formation of disulfide bonds.
1991,
Pubmed
Hull,
Integration of a small integral membrane protein, M2, of influenza virus into the endoplasmic reticulum: analysis of the internal signal-anchor domain of a protein with an ectoplasmic NH2 terminus.
1988,
Pubmed
Jan,
Voltage-sensitive ion channels.
1989,
Pubmed
Kumpf,
A mechanism for ion selectivity in potassium channels: computational studies of cation-pi interactions.
1993,
Pubmed
Lamb,
Evidence for a ninth influenza viral polypeptide.
1978,
Pubmed
Lamb,
Spliced and unspliced messenger RNAs synthesized from cloned influenza virus M DNA in an SV40 vector: expression of the influenza virus membrane protein (M1).
1982,
Pubmed
Lamb,
Sequences of mRNAs derived from genome RNA segment 7 of influenza virus: colinear and interrupted mRNAs code for overlapping proteins.
1981,
Pubmed
Lamb,
Synthesis of influenza virus proteins in infected cells: translation of viral polypeptides, including three P polypeptides, from RNA produced by primary transcription.
1976,
Pubmed
Lamb,
Influenza virus M2 protein is an integral membrane protein expressed on the infected-cell surface.
1985,
Pubmed
Lamb,
Identification of a second protein (M2) encoded by RNA segment 7 of influenza virus.
1981,
Pubmed
Laskey,
Quantitative film detection of 3H and 14C in polyacrylamide gels by fluorography.
1975,
Pubmed
Miller,
Hunting for the pore of voltage-gated channels.
1992,
Pubmed
Ng,
Intracellular maturation and transport of the SV5 type II glycoprotein hemagglutinin-neuraminidase: specific and transient association with GRP78-BiP in the endoplasmic reticulum and extensive internalization from the cell surface.
1989,
Pubmed
Ohuchi,
Rescue of vector-expressed fowl plague virus hemagglutinin in biologically active form by acidotropic agents and coexpressed M2 protein.
1994,
Pubmed
Olmsted,
The 1A protein of respiratory syncytial virus is an integral membrane protein present as multiple, structurally distinct species.
1989,
Pubmed
Paterson,
Ability of the hydrophobic fusion-related external domain of a paramyxovirus F protein to act as a membrane anchor.
1987,
Pubmed
Paterson,
RNA editing by G-nucleotide insertion in mumps virus P-gene mRNA transcripts.
1990,
Pubmed
Pinto,
Influenza virus M2 protein has ion channel activity.
1992,
Pubmed
,
Xenbase
Pragnell,
Estrogen induction of a small, putative K+ channel mRNA in rat uterus.
1990,
Pubmed
,
Xenbase
Sanger,
DNA sequencing with chain-terminating inhibitors.
1977,
Pubmed
Sansom,
Influenza virus M2 protein: a molecular modelling study of the ion channel.
1993,
Pubmed
Sugimoto,
Immunohistochemical study of a rat membrane protein which induces a selective potassium permeation: its localization in the apical membrane portion of epithelial cells.
1990,
Pubmed
,
Xenbase
Sugrue,
Structural characteristics of the M2 protein of influenza A viruses: evidence that it forms a tetrameric channel.
1991,
Pubmed
Sugrue,
Specific structural alteration of the influenza haemagglutinin by amantadine.
1990,
Pubmed
Takeuchi,
Influenza virus M2 protein ion channel activity stabilizes the native form of fowl plague virus hemagglutinin during intracellular transport.
1994,
Pubmed
Takumi,
Cloning of a membrane protein that induces a slow voltage-gated potassium current.
1988,
Pubmed
,
Xenbase
Wang,
Ion channel activity of influenza A virus M2 protein: characterization of the amantadine block.
1993,
Pubmed
,
Xenbase
Williams,
Determination of the orientation of an integral membrane protein and sites of glycosylation by oligonucleotide-directed mutagenesis: influenza B virus NB glycoprotein lacks a cleavable signal sequence and has an extracellular NH2-terminal region.
1986,
Pubmed
Williams,
Polylactosaminoglycan modification of a small integral membrane glycoprotein, influenza B virus NB.
1988,
Pubmed
Zebedee,
Influenza A virus M2 protein: monoclonal antibody restriction of virus growth and detection of M2 in virions.
1988,
Pubmed
Zebedee,
Characterization of the influenza virus M2 integral membrane protein and expression at the infected-cell surface from cloned cDNA.
1985,
Pubmed
