Atomic structures of closed and open influenza B M2 proton channel reveal the conduction mechanism

Area of Science:

• Structural biology
• Virology
• Biophysics

Background:

• Influenza B virus relies on its M2 proton channel (BM2) for uncoating.
• BM2 facilitates viral entry, unlike the related influenza A M2 (AM2) channel.
• BM2 exhibits bidirectional proton conduction, distinct from AM2's rectification.

Purpose of the Study:

• To elucidate the structural mechanism of BM2 channel activation.
• To understand the molecular basis of BM2's bidirectional proton transport.
• To compare BM2 activation with the known mechanism of AM2.

Main Methods:

• Solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy.
• Determination of high-resolution structures (1.4- and 1.5-Å) of BM2 transmembrane domain.
• Analysis of channel conformational changes in a phospholipid environment.

Main Results:

• Revealed distinct closed and open states of the BM2 channel.
• Identified a 6° increase in transmembrane helix tilt angle upon activation.
• Observed a 2.1 Å increase in average pore diameter, indicating a scissor-like motion.
• Demonstrated that BM2 activation involves a symmetric scissor motion, contrasting AM2's alternating-access mechanism.

Conclusions:

• BM2 activation utilizes a scissor motion, enabling bidirectional proton flow.
• Asymmetric proton conduction relies on backbone hinge motion, while bidirectional flow uses symmetric scissor motion.
• Side chain dynamics of histidine and tryptophan are crucial for proton shuttling in BM2, similar to AM2.