Twisting gating residues in the Orai pore

Area of Science:

• Biophysics
• Molecular Biology
• Cell Physiology

Background:

• Store-operated calcium channels (Orai1-3) possess unique, elongated, funnel-shaped pore structures.
• Unlike classical channels, Orai channels have a distinct hydrophobic segment within the pore that regulates gating.
• Understanding Orai channel gating is crucial for cellular calcium signaling.

Purpose of the Study:

• To comment on recent findings regarding the gating mechanism of Orai channels.
• To highlight the role of specific residue interactions in controlling Orai channel conformation.
• To discuss the structural basis of Orai channel function.

Main Methods:

• Commentary on existing structural and functional data.
• Analysis of molecular interactions within the Orai channel pore.
• Interpretation of recent experimental results on Orai channel gating.

Main Results:

• Orai channels exhibit an unusual pore architecture.
• A hydrophobic segment within the Orai pore is a key determinant of channel gating.
• Decisive binding between three specific residues controls the open and closed states of Orai channels.

Conclusions:

• The gating mechanism of Orai channels is governed by specific residue interactions within the pore.
• The unique structural features of Orai channels, including the hydrophobic segment, are critical for their function.
• Recent work provides significant insight into the conformational control of Orai channel activity.