KcsA

KcsA is a prokaryotic potassium channel protein originally identified in Streptomyces lividans. It forms a homotetrameric channel that conducts potassium ions across the cell membrane. Each subunit contains two transmembrane helices (M1 and M2) separated by a pore loop that houses the highly conserved selectivity filter motif, typically expressed as TVGYG. The four subunits assemble to create a central ion-conducting pore with the selectivity filter lining the outer part and coordinating K+ ions as they pass through.

KcsA is gated by intracellular pH: it opens in acidic conditions and closes at neutral pH. The gating involves gating at the cytoplasmic side, traditionally described as a bundle crossing formed by the inner helices, and protonation of specific residues acts as the pH sensor. Although structurally simple, KcsA shares essential features with more complex voltage-gated potassium channels, and it has been instrumental in understanding how a pore-forming region can achieve high selectivity for K+ while excluding Na+.

Structurally, KcsA was the subject of a landmark crystal structure published in 1998 by the MacKinnon group, providing the first high-resolution view of a potassium channel and detailing the architecture of the selectivity filter and the overall pore. The structure helped establish the knock-on mechanism by which multiple K+ ions occupy the filter and pass through with high efficiency.

As a model system, KcsA has become a foundational tool in studies of ion selectivity, conduction, and gating in potassium channels. It is widely used in structural biology, biophysics, and biochemistry to illustrate principles applicable to the broader K+ channel family.