Salt bridges in the miniature viral channel Kcv are important for function

Abstract

The viral potassium channel Kcv comprises only 94 amino acids, which represent the pore module of more complex K(+) channels. As for Kir-type channels, Kcv also has a short N-terminal helix exposed to the cytoplasm, upstream of the first transmembrane domain. Here we show that this helix is relevant for Kcv function. The presence of charged amino acids, which form dynamic inter- and intra-subunit salt bridges is crucial. Electrophysiological measurements, yeast rescue experiments and molecular dynamics simulations show that mutants in which the critical salt bridge formation is impaired have no or reduced channel activity. We conclude that these salt bridges destabilise the complexation of K(+) ions by negative charges on the inner transmembrane domain at the entrance into the cavity. This feature facilitates a continuous and coordinated transfer of ions between the cavity and the cytoplasm for channels without the canonical bundle crossing.

Chloroviruses: not your everyday plant virus

“…While K + channels from prokaryotes and eukaryotes often consist of several hundred amino acids, Kcv from PBCV-1 consists of 94 amino acids [37] and virus ATCV-1 Kcv consists of 82 amino acids [38]. In spite of their small sizes, both viral proteins form functional channels that have many of the properties associated with larger K + channels such as selectivity, gating and sensitivity to inhibitors [39-42]. Kcv proteins readily assemble into tetramers and sort in cells to distinct target membranes [43].…”

“…Despite their small sizes, the virus proteins typically have all of the catalytic properties of larger enzymes. Their small size and the fact that they are often “laboratory friendly” have made them excellent models for mechanistic and structural studies (e.g., see [41,42]. …”

Potassium Ion Channels: Could They Have Evolved from Viruses?

“…For a tandem channel, two subunits are linked (blue line) by six Gly; a GFP (green oval) is fused to the C terminus. Currents were measured as described in Hertel et al (2010). The steady-state current/voltage (I/V) relation of measurements in A to C and E and F are plotted in D and H, respectively.…”

Exploring the Viral Channel KcvPBCV-1 Function via Computation

“…The slow modality was suggested to involve the TM1 segments: the movement of TM1 is coupled to that of the adjacent domains of the pore through salt bridges, and upon disruption of the salt bridges, TM1 interferes with the transport of potassium ions (Hertel et al. 2010; Gebhardt et al. 2011).…”