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Identification of the Pore-lining Residues of the BM2 Ion Channel Protein of Influenza B Virus.

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Title: Identification of the Pore-lining Residues of the BM2 Ion Channel Protein of Influenza B Virus.
Authors: Chunlong Ma1, Soto, Cinque S.2, Ohigashi, Yuki1, Taylor, Albert1, Bournas, Vasilios1, Glawe, Brett1, Udo, Maria K.3, Degrado, William F.2,4, Lamb, Robert A.5,6, Pint, Lawrence H.1 Iarry-pinto@northwestern.edu
Source: Journal of Biological Chemistry. 6/6/2008, Vol. 283 Issue 23, p15921-15931. 11p. 6 Graphs.
Subjects: Biochemistry, Ion channels, Endosomes, Influenza A virus, Proteins, Acidification
Abstract: The influenza B virus BM2 proton-selective ion channel is essential for virus uncoating, a process that occurs in the acidic environment of the endosome. The BM2 channel causes acidification of the interior of the virus particle, which results in dissociation of the viral membrane protein from the ribonucleo- protein core. The BM2 protein is similar to the A/M2 protein ion channel of influenza A virus (A/M2) in that it contains an HXXXW motif. Unlike the A/M2 protein, the BM2 protein is not inhibited by the antiviral drug amantadine. We used mutagenesis to ascertain the pore-lining residues of the BM2 ion channel. The specific activity (relative to wild type), reversal voltage, and susceptibility to modification by (2-aminoethyl)-methane thiosulfonate and N-ethylmaleimide of cysteine mutant proteins were measured in oocytes. It was found that mutation of transmembrane domain residues Ser9, Ser12, Phe13, Ser16, His19, and Trp23 to cysteine were most disruptive for ion channel function. These cysteine mutants were also most susceptible to (2- aminoethyl)-methane thiosulfonate and N-ethylmaleimide modification. Furthermore, considerable amounts of dimer were formed in the absence of oxidative reagents when cysteine was introduced at positions Ser9, Ser12, Ser16, or Trps23. Based on these experimental data, a BM2 transmembrane domain model is proposed. The presence of polar residues in the pore is a probable explanation for the amantadine insensitivity of the BM2 protein and suggests that related but more polar compounds might serve as useful inhibitors of the protein. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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DbLabel: Engineering Source
An: 32704317
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  Data: Identification of the Pore-lining Residues of the BM2 Ion Channel Protein of Influenza B Virus.
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  Data: <searchLink fieldCode="AR" term="%22Chunlong+Ma%22">Chunlong Ma</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Soto%2C+Cinque+S%2E%22">Soto, Cinque S.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Ohigashi%2C+Yuki%22">Ohigashi, Yuki</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Taylor%2C+Albert%22">Taylor, Albert</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Bournas%2C+Vasilios%22">Bournas, Vasilios</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Glawe%2C+Brett%22">Glawe, Brett</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Udo%2C+Maria+K%2E%22">Udo, Maria K.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Degrado%2C+William+F%2E%22">Degrado, William F.</searchLink><relatesTo>2,4</relatesTo><br /><searchLink fieldCode="AR" term="%22Lamb%2C+Robert+A%2E%22">Lamb, Robert A.</searchLink><relatesTo>5,6</relatesTo><br /><searchLink fieldCode="AR" term="%22Pint%2C+Lawrence+H%2E%22">Pint, Lawrence H.</searchLink><relatesTo>1</relatesTo><i> Iarry-pinto@northwestern.edu</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 6/6/2008, Vol. 283 Issue 23, p15921-15931. 11p. 6 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Biochemistry%22">Biochemistry</searchLink><br /><searchLink fieldCode="DE" term="%22Ion+channels%22">Ion channels</searchLink><br /><searchLink fieldCode="DE" term="%22Endosomes%22">Endosomes</searchLink><br /><searchLink fieldCode="DE" term="%22Influenza+A+virus%22">Influenza A virus</searchLink><br /><searchLink fieldCode="DE" term="%22Proteins%22">Proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Acidification%22">Acidification</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: The influenza B virus BM2 proton-selective ion channel is essential for virus uncoating, a process that occurs in the acidic environment of the endosome. The BM2 channel causes acidification of the interior of the virus particle, which results in dissociation of the viral membrane protein from the ribonucleo- protein core. The BM2 protein is similar to the A/M2 protein ion channel of influenza A virus (A/M2) in that it contains an HXXXW motif. Unlike the A/M2 protein, the BM2 protein is not inhibited by the antiviral drug amantadine. We used mutagenesis to ascertain the pore-lining residues of the BM2 ion channel. The specific activity (relative to wild type), reversal voltage, and susceptibility to modification by (2-aminoethyl)-methane thiosulfonate and N-ethylmaleimide of cysteine mutant proteins were measured in oocytes. It was found that mutation of transmembrane domain residues Ser9, Ser12, Phe13, Ser16, His19, and Trp23 to cysteine were most disruptive for ion channel function. These cysteine mutants were also most susceptible to (2- aminoethyl)-methane thiosulfonate and N-ethylmaleimide modification. Furthermore, considerable amounts of dimer were formed in the absence of oxidative reagents when cysteine was introduced at positions Ser9, Ser12, Ser16, or Trps23. Based on these experimental data, a BM2 transmembrane domain model is proposed. The presence of polar residues in the pore is a probable explanation for the amantadine insensitivity of the BM2 protein and suggests that related but more polar compounds might serve as useful inhibitors of the protein. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
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  Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1074/jbc.M710302200
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      – Code: eng
        Text: English
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        PageCount: 11
        StartPage: 15921
    Subjects:
      – SubjectFull: Biochemistry
        Type: general
      – SubjectFull: Ion channels
        Type: general
      – SubjectFull: Endosomes
        Type: general
      – SubjectFull: Influenza A virus
        Type: general
      – SubjectFull: Proteins
        Type: general
      – SubjectFull: Acidification
        Type: general
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      – TitleFull: Identification of the Pore-lining Residues of the BM2 Ion Channel Protein of Influenza B Virus.
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              M: 06
              Text: 6/6/2008
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