Chemistry of ion coordination and hydration revealed by a K+ channel–Fab complex at 2.0 Å resolution

Abstract

Ion transport proteins must remove an ion's hydration shell to coordinate the ion selectively on the basis of its size and charge. To discover how the K+ channel solves this fundamental aspect of ion conduction, we solved the structure of the KcsA K+ channel in complex with a monoclonal Fab antibody fragment at 2.0 A resolution. Here we show how the K+ channel displaces water molecules around an ion at its extracellular entryway, and how it holds a K+ ion in a square antiprism of water molecules in a cavity near its intracellular entryway. Carbonyl oxygen atoms within the selectivity filter form a very similar square antiprism around each K+ binding site, as if to mimic the waters of hydration. The selectivity filter changes its ion coordination structure in low K+ solutions. This structural change is crucial to the operation of the selectivity filter in the cellular context, where the K+ ion concentration near the selectivity filter varies in response to channel gating.

Molecular basis of ion permeability in a voltage‐gated sodium channel

“…Potassium channels have a very narrow tunnel forming direct connections to the K + through four backbone carbonyls, with no intervening water molecules. Apparently only two sites out of the four that have been identified can be occupied at any one time (Zhou et al , 2001; Jiang et al , 2002, 2003). In contrast, the prokaryotic sodium channel SF is wider and its mouth contains a highly conserved glutamate that would allow a hemi‐hydrated sodium ion to pass through.…”

Probing Conformational Changes during the Gating Cycle of a Potassium Channel in Lipid Bilayers

“…In addition to strong binding, subtle changes in lipid character and bilayer state can have significant effects on protein function, such as those observed for the bacterial KcsA potassium channel (3,10,11). Upon activation at acidic pH, KcsA mediates a transient K þ current that is characterized by a fast activation time course followed by a slow C-type inactivation process (12).…”

“…The resting state of the KcsA channel, with the inactivation gate open and the activation gate closed (closed-conductive state), and the inactivated state, with the inactivation gate closed and the activation gate open (open-inactivated state), are relatively long-lived. Therefore, conformational changes associated with the opening and closing of the KcsA activation and inactivation gates can be studied with the use of crystallographic (10,11,13,14) and spectroscopic methods. The inner KcsA helices form an important part of the conduction pathway.…”

The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture

“…It contains two homologous copies of a six-transmembrane (6-TM) domain, which has no sequence homology to the canonical tetrameric K + channels and lacks the TVGYG selectivity filter motif 2–4 . Present in a subset of bacteria and archaea, the prokaryotic TMEM175 contains only a single 6-TM domain and functions as a tetramer.…”

“…Since TMEM175 lacks the TVGYG motif and sequence homology to canonical 6-TM K + channels 2–4 , it is predicted to adopt a distinct structure and K + selectivity mechanism from classical K + channels. Present among some bacteria and archaea, the prokaryotic TMEM175 (bacTMEM175) contains a single copy of a 6-TM domain in each subunit (Extended Data Fig.…”