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Secrets in acidic environments: How does M2 activate under low pH conditions?
M2 protein plays a vital role in the replication of influenza virus. The M2 protein is located in the viral envelope of influenza A virus as a proton-selective virosome. The channel is a homotetramer composed of four identical M2 units and is activated at low pH.
M2 protein can form pores through a helical structure stabilized by disulfide bonds, a property that enables it to conduct protons efficiently.
M2 protein structure
The M2 protein unit of influenza A virus consists of 97 amino acid residues and is divided into three parts: the external N-terminal domain, the transmembrane segment and the internal C-terminal domain. The transmembrane segment forms the pore of the ion channel and is essential for the conduction of hydrogen ions. Important amino acid residues such as His37 (pH sensor) and Trp41 (gate) play an important role in this process.
Proton conduction and selectivity
M2 channels are highly selective for protons and their operation depends on a low pH environment. The amino acid residues of His37 are responsible for this proton selectivity and pH regulation function. When His37 is replaced by other amino acids, the proton-selective activity is lost and the channel may transport sodium and potassium ions.
M2 Features
M2 channel protein is an important component of the viral envelope and can form a highly selective, pH-regulated proton-conducting channel. It maintains the pH in the basal membrane where viruses enter and infect host cells.
Inhibition and drug resistance
The anti-influenza virus drug Amanatidine is a drug that specifically blocks the M2 H+ channel by binding itself inside the channel and preventing the normal conduction of protons. Over time, the virus has developed resistance to these drugs, which means new challenges for current treatments.
M2 protein of influenza B and C
Influenza B and influenza C viruses also encode proteins BM2 and CM2 with similar functions. Although they are not highly similar to M2 in sequence, they share similarities in structure and mechanism.
SummarySpecially, BM2 is completely insensitive to amanatidine and limanatidine, demonstrating the evolutionary uniqueness of influenza B viruses.
The operation of the M2 protein shows how the pathway changes in specific environments to facilitate the influenza virus life cycle and its infection of the host. Understanding these processes is not only important for virology research, but also helps in the development of new antiviral treatments. In future research, facing these challenges, how can we fully interpret the diversity and adaptability of viruses?
