Related Experiment Video

Updated: Jun 28, 2026

Multi-target Parallel Processing Approach for Gene-to-structure Determination of the Influenza Polymerase PB2 Subunit
22:10

Multi-target Parallel Processing Approach for Gene-to-structure Determination of the Influenza Polymerase PB2 Subunit

Published on: June 28, 2013

pH-induced conformational change of the influenza M2 protein C-terminal domain

Phuong A Nguyen1, Cinque S Soto, Alexei Polishchuk

  • 1Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, Pennsylvania 19081, USA.

Biochemistry
|August 30, 2008
PubMed

Insights

Influenza A M2 protein, a drug target, functions as a pH-activated proton channel. Spin labeling EPR revealed pH-dependent structural changes in the M2 peptide, highlighting Lys 49

Area of Science:

  • Structural Biology
  • Biophysics
  • Virology

Background:

  • Influenza A M2 protein is a pH-activated proton channel crucial for viral replication.
  • M2 protein is a validated drug target for antiviral therapies.

Purpose of the Study:

  • To investigate the pH-dependent structural dynamics of the M2 protein transmembrane domain.
  • To elucidate the role of specific residues, particularly Lys 49, in M2 channel function.

Main Methods:

  • Site-directed spin labeling (SDSL) coupled with Electron Paramagnetic Resonance (EPR) spectroscopy.
  • Electrophysiology to assess proton channel activity.

Main Results:

  • The M2 peptide forms a stable helical structure at both high and low pH.
  • Significant pH-induced alterations in the oligomeric arrangement of M2 monomers were observed.
  • Residue Lys 49 was identified as critical for M2 channel function based on EPR and electrophysiology data.

Conclusions:

  • The M2 protein undergoes pH-dependent conformational changes affecting its tetrameric assembly.
  • Lys 49 plays a pivotal role in the proton channel activity of the M2 protein, suggesting its potential as a therapeutic target.

More Related Videos

Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein09:39

Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein

Published on: April 21, 2015

A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation07:53

A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation

Published on: January 9, 2019

Related Concept Videos

Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
Protein Folding01:25

Protein Folding

Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Influenza01:27

Influenza

Influenza is an acute, highly communicable viral disease that affects the respiratory tract and is responsible for seasonal epidemics worldwide. Influenza A is the most prevalent type associated with widespread outbreaks and is subtyped based on two surface glycoproteins: hemagglutinin (H) and neuraminidase (N), as in H1N1. These glycoproteins are essential for viral infectivity, transmission, and immune recognition. Transmission occurs primarily through respiratory droplets and contaminated...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...