Bacterial mechanosensitive channel of large conductance (MscL) (MscL)

The Bacterial mechanosensitive channel of large conductance (MscL) is a highly conserved, pore-forming membrane protein found in most bacterial species, including significant human pathogens [1.1.1, 1.2.2]. It serves as a critical biological emergency release valve that protects the cell from lysis during sudden osmotic downshock by sensing increased membrane tension [1.1.2, 1.1.3]. When activated, MscL undergoes a large conformational change to open a non-selective pore approximately 30 Å in diameter, allowing the rapid efflux of cytoplasmic solutes to reduce turgor pressure [1.1.1, 1.3.1]. Because MscL is unique to microbes and absent in animal cells, it represents a promising therapeutic target for the development of novel antibiotics and adjuvants [1.2.1, 1.2.2]. Certain antibiotics, such as streptomycin, and experimental agonists like SCH-79797, have been shown to directly bind and activate the channel, leading to lethal membrane permeabilization [1.2.2, 1.4.1]. Furthermore, the opening of MscL can facilitate the entry of other antimicrobial agents into the bacterial cytoplasm, potentially overcoming some forms of drug resistance [1.2.4, 1.2.5]. Research into MscL agonists aims to exploit this mechanism to create potent, specific antibacterials with low rates of resistance [1.2.1, 1.4.1]. The channel's structure and gating mechanism have been extensively studied, providing a foundation for structure-based drug design [1.1.4, 1.3.2].

Other names

Large conductance mechanosensitive ion channel [1.1.1]MscL protein [1.1.4]Mechanosensitive channel of large conductance [1.1.2]

Agonist-induced channel activation leading to membrane permeabilization and cell death [1.2.2, 1.4.1]; facilitation of antibiotic uptake through the open pore [1.2.4, 1.2.5]